{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:36:35Z","timestamp":1785411395720,"version":"3.56.0"},"reference-count":165,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HD106285"],"award-info":[{"award-number":["HD106285"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"award":["HD106285"],"award-info":[{"award-number":["HD106285"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Uterine smooth muscle tumors (USMTs) represent a diverse group of neoplasms arising from the myometrium, ranging from benign uterine fibroids (leiomyomas) to highly aggressive uterine leiomyosarcoma. While genetic alterations contribute to tumor development, growing evidence highlights the crucial role of epigenetic regulation in shaping tumor behavior. Among these mechanisms, histone modification has emerged as a key regulator of chromatin structure and gene expression. Histone modifications, including acetylation, methylation, phosphorylation, ubiquitination, ADP-ribosylation, and SUMOylation, are dynamically controlled by epigenetic regulators known as writers, erasers, and readers, which collectively modulate transcriptional programs involved in cell proliferation, differentiation, and stress responses. Recent studies indicate that dysregulation of histone-modifying enzymes contributes to the pathogenesis of USMTs by altering chromatin accessibility and transcriptional networks. In uterine fibroids, histone modifications are associated with hormone-responsive signaling pathways, extracellular matrix deposition, and abnormal smooth muscle cell proliferation. In contrast, uterine leiomyosarcoma exhibits extensive epigenetic reprogramming characterized by aberrant histone acetylation and methylation patterns, dysregulated chromatin regulators, and activation of oncogenic signaling pathways that promote tumor aggressiveness and genomic instability. Importantly, histone modifications interact with other epigenetic mechanisms, including DNA methylation, non-coding RNA\u2013mediated regulation, and RNA epitranscriptomics, forming complex networks that influence tumor initiation and progression. This narrative review summarizes current knowledge on histone modification pathways and their roles in USMT biology, highlighting the functions of histone-modifying enzymes, their interactions with other epigenetic mechanisms, and their impact on tumor development. In addition, this review discusses emerging therapeutic strategies targeting epigenetic regulators, including inhibitors of histone deacetylases, histone methyltransferases, and readers, as well as potential epigenetic biomarkers for diagnosis and prognosis. Finally, this review outlines future research directions, including multi-omics integration, and advanced epigenomic technologies, which may provide deeper insights into the epigenetic landscape of USMTs and facilitate the development of personalized therapeutic approaches.<\/jats:p>","DOI":"10.3390\/biology15110838","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:36:56Z","timestamp":1779892616000},"page":"838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Regulation of Uterine Smooth Muscle Tumors: Histone Modifications in Uterine Fibroids and Leiomyosarcoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-8946","authenticated-orcid":false,"given":"Qiwei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S104","DOI":"10.1038\/modpathol.2015.139","article-title":"Practical issues in uterine pathology from banal to bewildering: The remarkable spectrum of smooth muscle neoplasia","volume":"29","author":"Oliva","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, Q., Madueke-Laveaux, O.S., Cun, H., Wlodarczyk, M., Garcia, N., Carvalho, K.C., and Al-Hendy, A. (2024). Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy. Cells, 13.","DOI":"10.3390\/cells13131106"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1056\/NEJMra1209993","article-title":"Uterine fibroids","volume":"369","author":"Bulun","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Satala, C.B., Patrichi, G., Gurau, A.M., Toma, A., Popazu, C., and Mihalache, D. (2026). An Update on Uterine Smooth Muscle Tumors: Is It a Leiomyoma, a STUMP, or a Leiomyosarcoma?. Biomedicines, 14.","DOI":"10.3390\/biomedicines14020285"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ygyno.2017.02.019","article-title":"Uterine leiomyosarcoma: Epidemiology, contemporary treatment strategies and the impact of uterine morcellation","volume":"145","author":"Ricci","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1126\/science.1208930","article-title":"MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas","volume":"334","author":"Makinen","year":"2011","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, K., Kim, S., Ahn, T., Kim, H., Shin, S.J., Choi, C.H., Park, S., Kim, Y.B., No, J.H., and Suh, D.H. (2023). A differential diagnosis between uterine leiomyoma and leiomyosarcoma using transcriptome analysis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11394-0"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1210\/endrev\/bnab039","article-title":"Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment","volume":"43","author":"Yang","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0140-6736(00)03622-9","article-title":"Uterine fibroids","volume":"357","author":"Stewart","year":"2001","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1289\/ehp.5787","article-title":"Etiology and pathogenesis of uterine leiomyomas: A review","volume":"111","author":"Flake","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, Q., and Al-Hendy, A. (2023). Update on the Role and Regulatory Mechanism of Extracellular Matrix in the Pathogenesis of Uterine Fibroids. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065778"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1210\/en.2009-1225","article-title":"Progesterone is essential for maintenance and growth of uterine leiomyoma","volume":"151","author":"Ishikawa","year":"2010","journal-title":"Endocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/humupd\/dmh019","article-title":"Sex steroidal regulation of uterine leiomyoma growth and apoptosis","volume":"10","author":"Maruo","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1067\/mob.2003.99","article-title":"High cumulative incidence of uterine leiomyoma in black and white women: Ultrasound evidence","volume":"188","author":"Baird","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1056\/NEJMoa1302736","article-title":"Characterization of uterine leiomyomas by whole-genome sequencing","volume":"369","author":"Mehine","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ng849","article-title":"Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer","volume":"30","author":"Tomlinson","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ponomarenko, M., Reshetnikov, E., Churnosova, M., Aristova, I., Abramova, M., Novakov, V., Churnosov, V., Polonikov, A., Plotnikov, D., and Churnosov, M. (2025). Genetic Variants Linked with the Concentration of Sex Hormone-Binding Globulin Correlate with Uterine Fibroid Risk. Life, 15.","DOI":"10.3390\/life15071150"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ponomarenko, M., Reshetnikov, E., Churnosova, M., Aristova, I., Abramova, M., Novakov, V., Churnosov, V., Polonikov, A., Churnosov, M., and Ponomarenko, I. (2025). Obesity\/Overweight as a Meaningful Modifier of Associations Between Gene Polymorphisms Affecting the Sex Hormone-Binding Globulin Content and Uterine Myoma. Life, 15.","DOI":"10.3390\/life15091459"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ponomareva, L., Dorofeeva, A., Samoylenko, J., Kobzeva, K., and Bushueva, O. (2025). Uterine Fibroids-Associated GWAS Loci and the Risk of Arterial Hypertension: A Pilot Study. Front. Biosci., 17.","DOI":"10.31083\/FBS42728"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ponomarenko, I., Reshetnikov, E., Polonikov, A., Verzilina, I., Sorokina, I., Yermachenko, A., Dvornyk, V., and Churnosov, M. (2020). Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.512940"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1007\/s43032-024-01727-0","article-title":"The Annual Economic Burden of Uterine Fibroids in the United States (2010 Versus 2022): A Comparative Cost-Analysis","volume":"31","author":"Hazimeh","year":"2024","journal-title":"Reprod. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1200\/JCO.2017.75.9845","article-title":"Soft Tissue and Uterine Leiomyosarcoma","volume":"36","author":"George","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/00000478-199406000-00001","article-title":"Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases","volume":"18","author":"Bell","year":"1994","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","article-title":"Chromatin modifications and their function","volume":"128","author":"Kouzarides","year":"2007","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg.2016.59","article-title":"The molecular hallmarks of epigenetic control","volume":"17","author":"Allis","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbagrm.2014.03.001","article-title":"Interpreting the language of histone and DNA modifications","volume":"1839","author":"Rothbart","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"a018762","DOI":"10.1101\/cshperspect.a018762","article-title":"Writers and readers of histone acetylation: Structure, mechanism, and inhibition","volume":"6","author":"Marmorstein","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nrm2145","article-title":"Histone acetyltransferase complexes: One size doesn\u2019t fit all","volume":"8","author":"Lee","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1126\/science.1124000","article-title":"Histone H4-K16 acetylation controls chromatin structure and protein interactions","volume":"311","author":"Ishii","year":"2006","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/j.celrep.2018.07.041","article-title":"Enhancer Activity Requires CBP\/P300 Bromodomain-Dependent Histone H3K27 Acetylation","volume":"24","author":"Raisner","year":"2018","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.molcel.2012.11.006","article-title":"Histone lysine methylation dynamics: Establishment, regulation, and biological impact","volume":"48","author":"Black","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1038\/emm.2017.11","article-title":"Writing, erasing and reading histone lysine methylations","volume":"49","author":"Hyun","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.molcel.2006.12.014","article-title":"Methylation of lysine 4 on histone H3: Intricacy of writing and reading a single epigenetic mark","volume":"25","author":"Ruthenburg","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nature09784","article-title":"The Polycomb complex PRC2 and its mark in life","volume":"469","author":"Margueron","year":"2011","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"50719","DOI":"10.18632\/oncotarget.9368","article-title":"SETD2: An epigenetic modifier with tumor suppressor functionality","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0092-8674(01)00542-6","article-title":"Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability","volume":"107","author":"Peters","year":"2001","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.4161\/epi.21975","article-title":"Histone phosphorylation: A chromatin modification involved in diverse nuclear events","volume":"7","author":"Rossetto","year":"2012","journal-title":"Epigenetics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.tig.2004.02.007","article-title":"Phosphorylation of histone H3: A balancing act between chromosome condensation and transcriptional activation","volume":"20","author":"Nowak","year":"2004","journal-title":"Trends Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1128\/MCB.22.3.874-885.2002","article-title":"Mitotic phosphorylation of histone H3: Spatio-temporal regulation by mammalian Aurora kinases","volume":"22","author":"Crosio","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","article-title":"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139","volume":"273","author":"Rogakou","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"42462","DOI":"10.1074\/jbc.C100466200","article-title":"ATM phosphorylates histone H2AX in response to DNA double-strand breaks","volume":"276","author":"Burma","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"47759","DOI":"10.1074\/jbc.C100569200","article-title":"Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress","volume":"276","author":"Ward","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.molcel.2008.02.014","article-title":"Histone ubiquitination: Triggering gene activity","volume":"29","author":"Weake","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbagrm.2014.01.002","article-title":"Writing and reading H2B monoubiquitylation","volume":"1839","author":"Fuchs","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nature02985","article-title":"Role of histone H2A ubiquitination in Polycomb silencing","volume":"431","author":"Wang","year":"2004","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/nrm4067","article-title":"Targeting Polycomb systems to regulate gene expression: Modifications to a complex story","volume":"16","author":"Blackledge","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.tcb.2011.06.001","article-title":"Histone ADP-ribosylation in DNA repair, replication and transcription","volume":"21","author":"Messner","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6043","DOI":"10.1093\/nar\/gkab280","article-title":"Histone sumoylation and chromatin dynamics","volume":"49","author":"Ryu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13225","DOI":"10.1073\/pnas.1735528100","article-title":"Histone sumoylation is associated with transcriptional repression","volume":"100","author":"Shiio","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41594-023-00977-x","article-title":"HPF1-dependent histone ADP-ribosylation triggers chromatin relaxation to promote the recruitment of repair factors at sites of DNA damage","volume":"30","author":"Smith","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103711","DOI":"10.1016\/j.dnarep.2024.103711","article-title":"PARticular MARks: Histone ADP-ribosylation and the DNA damage response","volume":"140","author":"Ozdemir","year":"2024","journal-title":"DNA Repair"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2006.12.010","article-title":"Dynamic regulation of histone lysine methylation by demethylases","volume":"25","author":"Shi","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.tcb.2010.08.011","article-title":"Histone demethylases in development and disease","volume":"20","author":"Pedersen","year":"2010","journal-title":"Trends Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"a018713","DOI":"10.1101\/cshperspect.a018713","article-title":"Erasers of histone acetylation: The histone deacetylase enzymes","volume":"6","author":"Seto","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nrd4154","article-title":"Histone lysine demethylases as targets for anticancer therapy","volume":"12","author":"Hojfeldt","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1042\/bj20021321","article-title":"Histone deacetylases (HDACs): Characterization of the classical HDAC family","volume":"370","author":"Caron","year":"2003","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/nrm2346","article-title":"The Rpd3\/Hda1 family of lysine deacetylases: From bacteria and yeast to mice and men","volume":"9","author":"Yang","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/nrg2485","article-title":"The many roles of histone deacetylases in development and physiology: Implications for disease and therapy","volume":"10","author":"Haberland","year":"2009","journal-title":"Nat. Rev. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1146\/annurev.pathol.4.110807.092250","article-title":"Mammalian sirtuins: Biological insights and disease relevance","volume":"5","author":"Haigis","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"16017","DOI":"10.1038\/npjamd.2016.17","article-title":"It takes two to tango: NAD(+) and sirtuins in aging\/longevity control","volume":"2","author":"Imai","year":"2016","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/j.cell.2004.12.012","article-title":"Histone demethylation mediated by the nuclear amine oxidase homolog LSD1","volume":"119","author":"Shi","year":"2004","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrg1945","article-title":"JmjC-domain-containing proteins and histone demethylation","volume":"7","author":"Klose","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1158\/0008-5472.CAN-12-4300","article-title":"KDM4\/JMJD2 histone demethylases: Epigenetic regulators in cancer cells","volume":"73","author":"Berry","year":"2013","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nature06145","article-title":"UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development","volume":"449","author":"Agger","year":"2007","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1101\/gad.1652908","article-title":"Erasing the methyl mark: Histone demethylases at the center of cellular differentiation and disease","volume":"22","author":"Cloos","year":"2008","journal-title":"Genes Dev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1038\/embor.2011.140","article-title":"USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1","volume":"12","author":"Atanassov","year":"2011","journal-title":"EMBO Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nature08966","article-title":"Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB","volume":"465","author":"Scheuermann","year":"2010","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10292","DOI":"10.1038\/ncomms10292","article-title":"BAP1\/ASXL1 recruitment and activation for H2A deubiquitination","volume":"7","author":"Sahtoe","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1038\/onc.2010.371","article-title":"Serine\/threonine phosphatases in the DNA damage response and cancer","volume":"29","author":"Peng","year":"2010","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/nrm3478","article-title":"Function and regulation of SUMO proteases","volume":"13","author":"Hickey","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1074\/jbc.M706734200","article-title":"PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites","volume":"283","author":"Haince","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3811","DOI":"10.1093\/nar\/gkz120","article-title":"Poly(ADP-ribosyl)ation by PARP1: Reaction mechanism and regulatory proteins","volume":"47","author":"Alemasova","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7665","DOI":"10.1093\/nar\/gkm933","article-title":"Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells","volume":"35","author":"Mortusewicz","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/nsmb1338","article-title":"How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers","volume":"14","author":"Taverna","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/47412","article-title":"The language of covalent histone modifications","volume":"403","author":"Strahl","year":"2000","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the histone code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1038\/nsmb.2436","article-title":"Perceiving the epigenetic landscape through histone readers","volume":"19","author":"Musselman","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/cr.2011.42","article-title":"Readers of histone modifications","volume":"21","author":"Yun","year":"2011","journal-title":"Cell Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1146\/annurev-biochem-061809-175347","article-title":"Signals and combinatorial functions of histone modifications","volume":"80","author":"Suganuma","year":"2011","journal-title":"Annu. Rev. Biochem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrd4286","article-title":"Targeting bromodomains: Epigenetic readers of lysine acetylation","volume":"13","author":"Filippakopoulos","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/20974","article-title":"Structure and ligand of a histone acetyltransferase bromodomain","volume":"399","author":"Dhalluin","year":"1999","journal-title":"Nature"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0014-5793(01)03309-9","article-title":"Bromodomain: An acetyl-lysine binding domain","volume":"513","author":"Zeng","year":"2002","journal-title":"FEBS Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8758","DOI":"10.1073\/pnas.1433065100","article-title":"The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis","volume":"100","author":"Dey","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.cell.2012.02.013","article-title":"Histone recognition and large-scale structural analysis of the human bromodomain family","volume":"149","author":"Filippakopoulos","year":"2012","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nrm1981","article-title":"Breaking barriers to transcription elongation","volume":"7","author":"Saunders","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/35065138","article-title":"Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain","volume":"410","author":"Bannister","year":"2001","journal-title":"Nature"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/35065132","article-title":"Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins","volume":"410","author":"Lachner","year":"2001","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature722","article-title":"Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9","volume":"416","author":"Nielsen","year":"2002","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1101\/gad.269603","article-title":"Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27","volume":"17","author":"Min","year":"2003","journal-title":"Genes Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrm2763","article-title":"Mechanisms of polycomb gene silencing: Knowns and unknowns","volume":"10","author":"Simon","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature04815","article-title":"A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling","volume":"442","author":"Wysocka","year":"2006","journal-title":"Nature"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cell.2007.08.016","article-title":"Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4","volume":"131","author":"Vermeulen","year":"2007","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1126\/science.1125162","article-title":"Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A","volume":"312","author":"Huang","year":"2006","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/nature08398","article-title":"Role of the polycomb protein EED in the propagation of repressive histone marks","volume":"461","author":"Margueron","year":"2009","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9061","DOI":"10.1093\/nar\/gkr613","article-title":"Handpicking epigenetic marks with PHD fingers","volume":"39","author":"Musselman","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1172\/JCI69738","article-title":"New and emerging HDAC inhibitors for cancer treatment","volume":"124","author":"West","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/bs.acr.2016.04.001","article-title":"Small-Molecule Targeting of BET Proteins in Cancer","volume":"131","author":"French","year":"2016","journal-title":"Adv. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nm.4036","article-title":"Targeting EZH2 in cancer","volume":"22","author":"Kim","year":"2016","journal-title":"Nat. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1095\/biolreprod.115.134924","article-title":"The Polycomb Group Protein EZH2 Impairs DNA Damage Repair Gene Expression in Human Uterine Fibroids","volume":"94","author":"Yang","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Yang, Q., Ali, M., Trevino, L.S., Mas, A., Ismail, N., and Al-Hendy, A. (2023). Epigenetic Modulation of Inflammatory Pathways in Myometrial Stem Cells and Risk of Uterine Fibroids. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411641"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.xfss.2023.05.003","article-title":"EZH2 activates Wnt\/beta-catenin signaling in human uterine fibroids, which is inhibited by the natural compound methyl jasmonate","volume":"4","author":"Ali","year":"2023","journal-title":"F&S Sci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s00018-023-04919-0","article-title":"Developmental reprogramming of myometrial stem cells by endocrine disruptor linking to risk of uterine fibroids","volume":"80","author":"Yang","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41586-021-03747-1","article-title":"Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma","volume":"596","author":"Berta","year":"2021","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"108927","DOI":"10.1016\/j.celrep.2021.108927","article-title":"Epigenomic tensor predicts disease subtypes and reveals constrained tumor evolution","volume":"34","author":"Leistico","year":"2021","journal-title":"Cell Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41467-020-14701-6","article-title":"Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas","volume":"11","author":"Moyo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Carbajo-Garcia, M.C., de Miguel-Gomez, L., Juarez-Barber, E., Trelis, A., Monleon, J., Pellicer, A., Flanagan, J.M., and Ferrero, H. (2022). Deciphering the Role of Histone Modifications in Uterine Leiomyoma: Acetylation of H3K27 Regulates the Expression of Genes Involved in Proliferation, Cell Signaling, Cell Transport, Angiogenesis and Extracellular Matrix Formation. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061279"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12958-023-01060-2","article-title":"H3K4me3 mediates uterine leiomyoma pathogenesis via neuronal processes, synapsis components, proliferation, and Wnt\/beta-catenin and TGF-beta pathways","volume":"21","author":"Faus","year":"2023","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1177\/1933719111398147","article-title":"Histone deacetylase 6 regulates estrogen receptor alpha in uterine leiomyoma","volume":"18","author":"Wei","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"e1517","DOI":"10.1210\/clinem\/dgz227","article-title":"Activation of beta-Catenin Signaling and its Crosstalk With Estrogen and Histone Deacetylases in Human Uterine Fibroids","volume":"105","author":"Ali","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.fertnstert.2021.10.012","article-title":"Histone deacetylase inhibition by suberoylanilide hydroxamic acid: A therapeutic approach to treat human uterine leiomyoma","volume":"117","author":"Corachan","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1177\/1933719116638186","article-title":"Identification of Polycomb Group Protein EZH2-Mediated DNA Mismatch Repair Gene MSH2 in Human Uterine Fibroids","volume":"23","author":"Yang","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Yang, Q., Vafaei, S., Falahati, A., Khosh, A., Bariani, M.V., Omran, M.M., Bai, T., Siblini, H., Ali, M., and He, C. (2024). Bromodomain-Containing Protein 9 Regulates Signaling Pathways and Reprograms the Epigenome in Immortalized Human Uterine Fibroid Cells. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020905"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s43032-024-01608-6","article-title":"Targeting Bromodomain-Containing Protein 9 in Human Uterine Fibroid Cells","volume":"32","author":"Yang","year":"2025","journal-title":"Reprod. Sci."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Yang, Q., Vafaei, S., Falahati, A., Khosh, A., Omran, M.M., Bai, T., Bariani, M.V., Ali, M., Boyer, T.G., and Al-Hendy, A. (2025). Decoding Bromodomain and Extra-Terminal Domain Protein-Mediated Epigenetic Mechanisms in Human Uterine Fibroids. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262412144"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Yang, Q., Falahati, A., Khosh, A., Lastra, R.R., Boyer, T.G., and Al-Hendy, A. (2024). Unraveling the Role of Bromodomain and Extra-Terminal Proteins in Human Uterine Leiomyosarcoma. Cells, 13.","DOI":"10.3390\/cells13171443"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/humupd\/dmaf005","article-title":"RNA modifications in female reproductive physiology and disease: Emerging roles and clinical implications","volume":"31","author":"Xiang","year":"2025","journal-title":"Hum. Reprod. Updat."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Yang, Q., Al-Hendy, A., and Boyer, T.G. (2026). Molecular Insights into Widespread Pseudouridine RNA Modifications: Implications for Women\u2019s Health and Disease. Biology, 15.","DOI":"10.3390\/biology15020142"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Yang, Q., Salih, S.M., Wu, R., Arora, I., Mousa, M., Al-Hendy, A., and Boyer, T.G. (2026). 5-Methylcytidine RNA Epitranscriptomics in Women\u2019s Health and Disease: Mechanisms and Clinical Implications. Cells, 15.","DOI":"10.3390\/cells15090847"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/ijc.34378","article-title":"Interplay between m(6) A epitranscriptome and epigenome in cancer: Current knowledge and therapeutic perspectives","volume":"153","author":"Bove","year":"2023","journal-title":"Int. J. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Willbanks, A., Wood, S., and Cheng, J.X. (2021). RNA Epigenetics: Fine-Tuning Chromatin Plasticity and Transcriptional Regulation, and the Implications in Human Diseases. Genes, 12.","DOI":"10.3390\/genes12050627"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ccell.2025.12.001","article-title":"Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications","volume":"44","author":"Deng","year":"2026","journal-title":"Cancer Cell"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yang, Q., Boyer, T.G., and Al-Hendy, A. (2025). Pseudouridine Synthase 7 in Cancer: Functions, Mechanisms, and Therapeutic Potential. Cells, 14.","DOI":"10.3390\/cells14171380"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Yang, Q., Diamond, M.P., and Al-Hendy, A. (2016). Early Life Adverse Environmental Exposures Increase the Risk of Uterine Fibroid Development: Role of Epigenetic Regulation. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00040"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.fertnstert.2016.08.023","article-title":"Endocrine-disrupting chemicals and uterine fibroids","volume":"106","author":"Katz","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1097\/MED.0000000000000578","article-title":"The role of endocrine-disrupting chemicals in uterine fibroid pathogenesis","volume":"27","author":"Bariani","year":"2020","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"368504231215601","DOI":"10.1177\/00368504231215601","article-title":"Endocrine-disrupting chemicals and epigenetic reprogramming in developmental origin of uterine fibroids","volume":"106","author":"Yang","year":"2023","journal-title":"Sci. Prog."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00109-020-01888-w","article-title":"Synergistic effects of pazopanib and hyperthermia against uterine leiomyosarcoma growth mediated by downregulation of histone acetyltransferase 1","volume":"98","author":"Lin","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Toyohara, Y., Sone, K., Kumegawa, K., Yamamoto, Y., Hachijo, R., Kukita, A., Taguchi, A., Ikemura, M., Miyamoto, Y., and Tanikawa, M. (2025). Synthetic lethality from the combination of a histone methyltransferase SUV39H2 inhibitor and a poly (ADP-ribose) polymerase inhibitor for uterine leiomyosarcoma. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-15267-6"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Guan, M., Wu, X., Chu, P., and Chow, W.A. (2017). Fatty acid synthase reprograms the epigenome in uterine leiomyosarcomas. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179692"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e70626","DOI":"10.1111\/jcmm.70626","article-title":"Dual Targeting EZH2 and Histone Deacetylases in Human Uterine Sarcoma Cells Under Both 2D and 3D Culture Conditions","volume":"29","author":"Omran","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/01.pas.0000188029.63706.31","article-title":"Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus","volume":"30","author":"Waltregny","year":"2006","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/jjco\/hyz059","article-title":"The combination of histone deacetylase and p53 expressions and histological subtype has prognostic implication in uterine leiomyosarcoma","volume":"49","author":"Baek","year":"2019","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Yang, Q., Bariani, M.V., Falahati, A., Khosh, A., Lastra, R.R., Siblini, H., Boyer, T.G., and Al-Hendy, A. (2022). The Functional Role and Regulatory Mechanism of Bromodomain-Containing Protein 9 in Human Uterine Leiomyosarcoma. Cells, 11.","DOI":"10.3390\/cells11142160"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Yang, Q., Falahati, A., Khosh, A., Mohammed, H., Kang, W., Corachan, A., Bariani, M.V., Boyer, T.G., and Al-Hendy, A. (2022). Targeting Class I Histone Deacetylases in Human Uterine Leiomyosarcoma. Cells, 11.","DOI":"10.3390\/cells11233801"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"110909","DOI":"10.1016\/j.ygeno.2024.110909","article-title":"Dissecting transposable elements and endogenous retroviruses upregulation by HDAC inhibitors in leiomyosarcoma cells: Implications for the interferon response","volume":"116","author":"Gualandi","year":"2024","journal-title":"Genomics"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2068517","DOI":"10.1155\/2018\/2068517","article-title":"SARC018_SPORE02: Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy","volume":"2018","author":"Choy","year":"2018","journal-title":"Sarcoma"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Makinen, N., Aavikko, M., Heikkinen, T., Taipale, M., Taipale, J., Koivisto-Korander, R., Butzow, R., and Vahteristo, P. (2016). Exome Sequencing of Uterine Leiomyosarcomas Identifies Frequent Mutations in TP53, ATRX, and MED12. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005850"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1002\/cncr.31754","article-title":"Loss of ATRX\/DAXX expression and alternative lengthening of telomeres in uterine leiomyomas","volume":"124","author":"Ahvenainen","year":"2018","journal-title":"Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.cell.2010.01.003","article-title":"Distinct factors control histone variant H3.3 localization at specific genomic regions","volume":"140","author":"Goldberg","year":"2010","journal-title":"Cell"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Pang, Y., Chen, X., Ji, T., Cheng, M., Wang, R., Zhang, C., Liu, M., Zhang, J., and Zhong, C. (2023). The Chromatin Remodeler ATRX: Role and Mechanism in Biology and Cancer. Cancers, 15.","DOI":"10.3390\/cancers15082228"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.celrep.2015.03.036","article-title":"ATRX Plays a Key Role in Maintaining Silencing at Interstitial Heterochromatic Loci and Imprinted Genes","volume":"11","author":"Voon","year":"2015","journal-title":"Cell Rep."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nsmb.2070","article-title":"Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin","volume":"18","author":"Eustermann","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Pfaff, M., Costa, P., Tang, H., Sailo, B., Sharma, A., and Ahuja, N. (2025). Decoding the Epigenome: Comparative Analysis of Uterine Leiomyosarcoma and Leiomyoma. Cancers, 17.","DOI":"10.3390\/cancers17162610"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1742-4658.2011.08089.x","article-title":"MicroRNAs and epigenetics","volume":"278","author":"Sato","year":"2011","journal-title":"FEBS J."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrg3074","article-title":"Non-coding RNAs in human disease","volume":"12","author":"Esteller","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"de Almeida, B.C., Dos Anjos, L.G., Dobroff, A.S., Baracat, E.C., Yang, Q., Al-Hendy, A., and Carvalho, K.C. (2022). Epigenetic Features in Uterine Leiomyosarcoma and Endometrial Stromal Sarcomas: An Overview of the Literature. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102567"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Yang, Q., and Al-Hendy, A. (2023). The Functional Role and Regulatory Mechanism of FTO m(6)A RNA Demethylase in Human Uterine Leiomyosarcoma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097957"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e2025182118","DOI":"10.1073\/pnas.2025182118","article-title":"Integrated mutational landscape analysis of uterine leiomyosarcomas","volume":"118","author":"Choi","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s13148-023-01574-x","article-title":"Single-cell sequencing technology applied to epigenetics for the study of tumor heterogeneity","volume":"15","author":"Hu","year":"2023","journal-title":"Clin. Epigenetics"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.trecan.2022.06.005","article-title":"Single cell cancer epigenetics","volume":"8","author":"Esteller","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13059-016-1133-7","article-title":"Single-cell epigenomic variability reveals functional cancer heterogeneity","volume":"18","author":"Litzenburger","year":"2017","journal-title":"Genome Biol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"S124","DOI":"10.1016\/j.ajog.2024.08.037","article-title":"Uterine fibroids at single-cell resolution: Unveiling cellular heterogeneity to improve understanding of pathogenesis and guide future therapies","volume":"232","author":"Goad","year":"2025","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1093\/humrep\/deac183","article-title":"Single-cell sequencing reveals novel cellular heterogeneity in uterine leiomyomas","volume":"37","author":"Goad","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1038\/s41467-024-45382-0","article-title":"Integrating leiomyoma genetics, epigenomics, and single-cell transcriptomics reveals causal genetic variants, genes, and cell types","volume":"15","author":"Buyukcelebi","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Guo, Y., Shen, D., Xiao, Y., Wu, C., Chen, M., Yang, L., Li, H., Tong, X., Chen, R., and Li, F. (2025). Single-cell profiling delineates the tumor microenvironment and immunological networks in patient-derived uterine leiomyosarcoma. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1653096"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"eadk9217","DOI":"10.1126\/science.adk9217","article-title":"Single-cell chromatin accessibility reveals malignant regulatory programs in primary human cancers","volume":"385","author":"Sundaram","year":"2024","journal-title":"Science"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1038\/s43018-025-01039-5","article-title":"Spatiotemporal analyses of the pan-cancer single-cell landscape reveal widespread profibrotic ecotypes associated with tumor immunity","volume":"6","author":"Han","year":"2025","journal-title":"Nat. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s12943-025-02426-3","article-title":"Single-cell multi-omics in cancer immunotherapy: From tumor heterogeneity to personalized precision treatment","volume":"24","author":"Le","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_161","first-page":"471","article-title":"CRISPR-Mediated Epigenome Editing","volume":"89","author":"Enriquez","year":"2016","journal-title":"Yale J. Biol. Med."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/nmeth.3630","article-title":"Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements","volume":"12","author":"Thakore","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nbt.3853","article-title":"CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome","volume":"35","author":"Klann","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nmeth.3325","article-title":"Functional annotation of native enhancers with a Cas9-histone demethylase fusion","volume":"12","author":"Kearns","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41556-020-00620-7","article-title":"CRISPR technologies for precise epigenome editing","volume":"23","author":"Nakamura","year":"2021","journal-title":"Nat. Cell Biol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/11\/838\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:22:45Z","timestamp":1780028565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/11\/838"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":165,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["biology15110838"],"URL":"https:\/\/doi.org\/10.3390\/biology15110838","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}