{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:12:13Z","timestamp":1776197533053,"version":"3.50.1"},"reference-count":100,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":48,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Shenzhen Medical Research Fund","award":["B2302026"],"award-info":[{"award-number":["B2302026"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFA1104500"],"award-info":[{"award-number":["2022YFA1104500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370392"],"award-info":[{"award-number":["82370392"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32300946"],"award-info":[{"award-number":["32300946"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Innovation Commission","doi-asserted-by":"publisher","award":["RCJC20210706091947009"],"award-info":[{"award-number":["RCJC20210706091947009"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Innovation Commission","doi-asserted-by":"publisher","award":["RCBS20221008093333076"],"award-info":[{"award-number":["RCBS20221008093333076"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Shenzhen Science and Technology Innovation Commission","doi-asserted-by":"publisher","award":["JCYJ20240813151803005"],"award-info":[{"award-number":["JCYJ20240813151803005"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund","award":["2023-I2M-1-003"],"award-info":[{"award-number":["2023-I2M-1-003"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund","award":["2023-I2M-2-003"],"award-info":[{"award-number":["2023-I2M-2-003"]}]},{"name":"Chinese Academy of Medical Sciences Innovation Fund","award":["2022-I2M-2-001"],"award-info":[{"award-number":["2022-I2M-2-001"]}]},{"name":"National High Level Hospital Clinical Research","award":["2025-GSP-GG-34"],"award-info":[{"award-number":["2025-GSP-GG-34"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>EZH2 catalyzes H3K27me3\u00a0and is essential for embryonic development. Although multiple EZH2 variants have been identified, the functional implications and physiological significance of its heterogeneity remain unclear. Here, we revealed that conserved cryptic splice sites generated two EZH2 variants with (EZH2A) or without (EZH2B) a 27-nt region, coding for a 9-aa segment. Structural modeling showed that splice-in or splice-off of the 9-aa segment caused a topological change in EZH2 structure. The 9-aa surplus in EZH2A strengthened its interaction with other PRC2 components, particularly in PRC2.2 holocomplex. We developed point-mutation mouse lines specifically depleting EZH2A or EZH2B (Ezh2amut or Ezh2bmut). Biallelic deletion of Ezh2a caused developmental defects and embryonic lethality between E12.5 and E15.5, while the Ezh2bmut mice were fertile and developed normally. Combined RNA-seq and CUT&amp;Tag analyses in mouse embryonic fibroblasts revealed that EZH2A and EZH2B bound to different genomic loci and affected H3K27me3 deposition in different subsets of genes related to development or the innate immune system, respectively. EZH2A depletion specifically suppressed the expression of genes involved in the development-related Hippo-Yap1 pathway, which might be attributable to a compensatory process mediated by JARID2. Our findings demonstrate that EZH2 heterogeneity from the 9-aa splicing event plays a crucial role in development.<\/jats:p>","DOI":"10.1093\/nar\/gkaf869","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T11:31:02Z","timestamp":1755603062000},"source":"Crossref","is-referenced-by-count":1,"title":["EZH2 variants derived from cryptic splice sites govern distinct epigenetic patterns during embryonic development"],"prefix":"10.1093","volume":"53","author":[{"given":"Ningning","family":"Guo","sequence":"first","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]},{"name":"Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen\u00a0518055 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongchao","family":"Zhan","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Lv","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]},{"name":"Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences , Shenzhen\u00a0518055 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Fang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajie","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junmei","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Die","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingqing","family":"Yan","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1800-2384","authenticated-orcid":false,"given":"Zhihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Shenzhen Hospital, Chinese Academy of Medical Sciences , Shenzhen\u00a0518057 ,","place":["China"]},{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing\u00a0100037 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"2025102300111791300_B1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature23263","article-title":"Allelic reprogramming of 3D chromatin architecture during early mammalian development","volume":"547","author":"Du","year":"2017","journal-title":"Nature"},{"key":"2025102300111791300_B2","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.cell.2016.05.050","article-title":"Establishing chromatin regulatory landscape during mouse preimplantation development","volume":"165","author":"Lu","year":"2016","journal-title":"Cell"},{"key":"2025102300111791300_B3","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.tcb.2014.09.006","article-title":"Reprogramming the genome to totipotency in mouse embryos","volume":"25","author":"Zhou","year":"2015","journal-title":"Trends Cell Biol"},{"key":"2025102300111791300_B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.gde.2015.06.003","article-title":"Unwind and transcribe: chromatin reprogramming in the early mammalian embryo","volume":"34","author":"Biechele","year":"2015","journal-title":"Curr Opin Genet Dev"},{"key":"2025102300111791300_B5","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.devcel.2017.07.026","article-title":"Zygotic genome activation in vertebrates","volume":"42","author":"Jukam","year":"2017","journal-title":"Dev Cell"},{"key":"2025102300111791300_B6","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrm3885","article-title":"Chromatin dynamics in the regulation of cell fate allocation during early embryogenesis","volume":"15","author":"Burton","year":"2014","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025102300111791300_B7","doi-asserted-by":"publisher","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":"2025102300111791300_B8","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes Dev"},{"key":"2025102300111791300_B9","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1101\/gad.321174.118","article-title":"Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program","volume":"33","author":"Eckersley-Maslin","year":"2019","journal-title":"Genes Dev"},{"key":"2025102300111791300_B10","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.tcb.2017.10.008","article-title":"Epigenome in early mammalian development: inheritance, reprogramming and establishment","volume":"28","author":"Xu","year":"2018","journal-title":"Trends Cell Biol"},{"key":"2025102300111791300_B11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41580-019-0151-1","article-title":"Roles and regulation of histone methylation in animal development","volume":"20","author":"Jambhekar","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025102300111791300_B12","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/s41580-019-0159-6","article-title":"The diverse roles of DNA methylation in mammalian development and disease","volume":"20","author":"Greenberg","year":"2019","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025102300111791300_B13","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1126\/science.1076997","article-title":"Role of histone H3 lysine 27 methylation in polycomb-group silencing","volume":"298","author":"Cao","year":"2002","journal-title":"Science"},{"key":"2025102300111791300_B14","doi-asserted-by":"publisher","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":"2025102300111791300_B15","doi-asserted-by":"publisher","first-page":"3769","DOI":"10.1128\/MCB.01432-06","article-title":"The polycomb group protein Suz12 is required for embryonic stem cell differentiation","volume":"27","author":"Pasini","year":"2007","journal-title":"Mol Cell Biol"},{"key":"2025102300111791300_B16","doi-asserted-by":"publisher","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":"2025102300111791300_B17","doi-asserted-by":"publisher","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":"2025102300111791300_B18","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/nm.4179","article-title":"The long noncoding RNA Chaer defines an epigenetic checkpoint in cardiac hypertrophy","volume":"22","author":"Wang","year":"2016","journal-title":"Nat Med"},{"key":"2025102300111791300_B19","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13072-016-0086-0","article-title":"Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3","volume":"9","author":"Prickaerts","year":"2016","journal-title":"Epigenetics Chromatin"},{"key":"2025102300111791300_B20","doi-asserted-by":"publisher","first-page":"7415","DOI":"10.1093\/nar\/gkr416","article-title":"ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity","volume":"39","author":"Young","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B21","doi-asserted-by":"publisher","first-page":"11316","DOI":"10.1038\/ncomms11316","article-title":"Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2","volume":"7","author":"Justin","year":"2016","journal-title":"Nat Commun"},{"key":"2025102300111791300_B22","doi-asserted-by":"publisher","first-page":"aac4383","DOI":"10.1126\/science.aac4383","article-title":"Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2","volume":"350","author":"Jiao","year":"2015","journal-title":"Science"},{"key":"2025102300111791300_B23","doi-asserted-by":"publisher","first-page":"11384","DOI":"10.1038\/ncomms11384","article-title":"Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance","volume":"7","author":"Brooun","year":"2016","journal-title":"Nat Commun"},{"key":"2025102300111791300_B24","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1016\/j.molcel.2008.11.004","article-title":"Ezh1 and Ezh2 maintain repressive chromatin through different mechanisms","volume":"32","author":"Margueron","year":"2008","journal-title":"Mol Cell"},{"key":"2025102300111791300_B25","doi-asserted-by":"publisher","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":"2025102300111791300_B26","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.molcel.2018.01.039","article-title":"Unique structural platforms of Suz12 dictate distinct classes of PRC2 for chromatin binding","volume":"69","author":"Chen","year":"2018","journal-title":"Mol Cell"},{"key":"2025102300111791300_B27","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/j.molcel.2019.12.019","article-title":"A dimeric structural scaffold for PRC2-PCL targeting to CpG island chromatin","volume":"77","author":"Chen","year":"2020","journal-title":"Mol Cell"},{"key":"2025102300111791300_B28","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41594-018-0036-6","article-title":"Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2","volume":"25","author":"Hojfeldt","year":"2018","journal-title":"Nat Struct Mol Biol"},{"key":"2025102300111791300_B29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.molcel.2019.03.011","article-title":"Molecular mechanisms directing PRC2 recruitment and H3K27 methylation","volume":"74","author":"Laugesen","year":"2019","journal-title":"Mol Cell"},{"key":"2025102300111791300_B30","first-page":"243","article-title":"The roles of EZH2 in cell lineage commitment","volume":"3","author":"Chou","year":"2011","journal-title":"Am J Transl Res"},{"key":"2025102300111791300_B31","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1071\/RD13169","article-title":"EZH2 is essential for development of mouse preimplantation embryos","volume":"26","author":"Huang","year":"2014","journal-title":"Reprod Fertil Dev"},{"key":"2025102300111791300_B32","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.theriogenology.2019.04.007","article-title":"Effect of EZH2 knockdown on preimplantation development of porcine parthenogenetic embryos","volume":"132","author":"Cai","year":"2019","journal-title":"Theriogenology"},{"key":"2025102300111791300_B33","doi-asserted-by":"publisher","first-page":"e31005","DOI":"10.1371\/journal.pone.0031005","article-title":"Conditional ablation of Ezh2 in murine hearts reveals its essential roles in endocardial cushion formation, cardiomyocyte proliferation and survival","volume":"7","author":"Chen","year":"2012","journal-title":"PLoS One"},{"key":"2025102300111791300_B34","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nrm.2017.27","article-title":"Alternative splicing as a regulator of development and tissue identity","volume":"18","author":"Baralle","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2025102300111791300_B35","doi-asserted-by":"publisher","first-page":"69","DOI":"10.7150\/ijbs.28129","article-title":"Identification and functional characterization of a new splicing variant of EZH2 in the central nervous system","volume":"15","author":"Li","year":"2019","journal-title":"Int J Biol Sci"},{"key":"2025102300111791300_B36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13072-018-0242-9","article-title":"EZH2 variants differentially regulate polycomb repressive complex 2 in histone methylation and cell differentiation","volume":"11","author":"Mu","year":"2018","journal-title":"Epigenetics Chromatin"},{"key":"2025102300111791300_B37","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.leukres.2017.10.015","article-title":"Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-methylation in myelodysplastic syndrome","volume":"63","author":"Shirahata-Adachi","year":"2017","journal-title":"Leuk Res"},{"key":"2025102300111791300_B38","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/978-1-4939-1215-5_13","article-title":"Isolation and handling of mouse embryonic fibroblasts","volume":"1194","author":"Jain","year":"2014","journal-title":"Methods Mol Biol"},{"key":"2025102300111791300_B39","doi-asserted-by":"publisher","first-page":"e107","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp","volume":"2","author":"Chen","year":"2023","journal-title":"Imeta"},{"key":"2025102300111791300_B40","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","article-title":"Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype","volume":"37","author":"Kim","year":"2019","journal-title":"Nat Biotechnol"},{"key":"2025102300111791300_B41","doi-asserted-by":"publisher","first-page":"e1009730","DOI":"10.1371\/journal.pcbi.1009730","article-title":"Improved transcriptome assembly using a hybrid of long and short reads with StringTie","volume":"18","author":"Shumate","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2025102300111791300_B42","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"2025102300111791300_B43","doi-asserted-by":"publisher","first-page":"W415","DOI":"10.1093\/nar\/gkae456","article-title":"WebGestalt 2024: faster gene set analysis and new support for metabolomics and multi-omics","volume":"52","author":"Elizarraras","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B44","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"2025102300111791300_B45","doi-asserted-by":"publisher","first-page":"W160","DOI":"10.1093\/nar\/gkw257","article-title":"deepTools2: a next generation web server for deep-sequencing data analysis","volume":"44","author":"Ramirez","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B46","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","article-title":"Model-based analysis of ChIP-Seq (MACS)","volume":"9","author":"Zhang","year":"2008","journal-title":"Genome Biol"},{"key":"2025102300111791300_B47","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1093\/bioinformatics\/btv145","article-title":"ChIPseeker: an R\/Bioconductor package for ChIP peak annotation, comparison and visualization","volume":"31","author":"Yu","year":"2015","journal-title":"Bioinformatics"},{"key":"2025102300111791300_B48","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1186\/1471-2105-11-237","article-title":"ChIPpeakAnno: a bioconductor package to annotate ChIP-seq and ChIP-chip data","volume":"11","author":"Zhu","year":"2010","journal-title":"BMC Bioinf"},{"key":"2025102300111791300_B49","doi-asserted-by":"publisher","first-page":"4319","DOI":"10.1038\/s41598-019-40738-9","article-title":"Ezh1 arises from Ezh2 gene duplication but its function is not required for zebrafish development","volume":"9","author":"Volkel","year":"2019","journal-title":"Sci Rep"},{"key":"2025102300111791300_B50","doi-asserted-by":"crossref","first-page":"9928","DOI":"10.1021\/acs.jmedchem.6b01315","article-title":"Identification of (R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a potent and selective inhibitor of histone methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-cell lymphomas","volume":"59","author":"Vaswani","year":"2016","journal-title":"J Med Chem"},{"key":"2025102300111791300_B51","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1126\/science.aar5700","article-title":"Structures of human PRC2 with its cofactors AEBP2 and JARID2","volume":"359","author":"Kasinath","year":"2018","journal-title":"Science"},{"key":"2025102300111791300_B52","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1093\/nar\/gkac047","article-title":"The transcriptional elongation factor CTR9 demarcates PRC2-mediated H3K27me3 domains by altering PRC2 subtype equilibrium","volume":"50","author":"Chan","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B53","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.molcel.2023.03.018","article-title":"PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1","volume":"83","author":"Glancy","year":"2023","journal-title":"Mol Cell"},{"key":"2025102300111791300_B54","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.molcel.2019.08.012","article-title":"PRC2.1 and PRC2.2 synergize to coordinate H3K27 trimethylation","volume":"76","author":"Healy","year":"2019","journal-title":"Mol Cell"},{"key":"2025102300111791300_B55","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.molcel.2018.03.005","article-title":"A family of vertebrate-specific polycombs encoded by the LCOR\/LCORL genes balance PRC2 subtype activities","volume":"70","author":"Conway","year":"2018","journal-title":"Mol Cell"},{"key":"2025102300111791300_B56","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1016\/j.molcel.2021.03.038","article-title":"Distinct PRC2 subunits regulate maintenance and establishment of Polycomb repression during differentiation","volume":"81","author":"Petracovici","year":"2021","journal-title":"Mol Cell"},{"key":"2025102300111791300_B57","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.molcel.2020.11.044","article-title":"Competition between PRC2.1 and 2.2 subcomplexes regulates PRC2 chromatin occupancy in human stem cells","volume":"81","author":"Youmans","year":"2021","journal-title":"Mol Cell"},{"key":"2025102300111791300_B58","doi-asserted-by":"publisher","first-page":"4330","DOI":"10.1128\/MCB.21.13.4330-4336.2001","article-title":"The polycomb-group gene Ezh2 is required for early mouse development","volume":"21","author":"O\u2019Carroll","year":"2001","journal-title":"Mol Cell Biol"},{"key":"2025102300111791300_B59","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.devcel.2023.11.029","article-title":"YAP and TAZ couple osteoblast precursor mobilization to angiogenesis and mechanoregulation in murine bone development","volume":"59","author":"Collins","year":"2024","journal-title":"Dev Cell"},{"key":"2025102300111791300_B60","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.yjmcc.2021.03.005","article-title":"YAP1\/TEAD1 upregulate platelet-derived growth factor receptor beta to promote vascular smooth muscle cell proliferation and neointima formation","volume":"156","author":"Osman","year":"2021","journal-title":"J Mol Cell Cardiol"},{"key":"2025102300111791300_B61","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bbrc.2018.05.196","article-title":"Yap1\/Taz are essential for the liver development in zebrafish","volume":"503","author":"Yi","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"2025102300111791300_B62","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1038\/s41556-020-00602-9","article-title":"Heat stress activates YAP\/TAZ to induce the heat shock transcriptome","volume":"22","author":"Luo","year":"2020","journal-title":"Nat Cell Biol"},{"key":"2025102300111791300_B63","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"2025102300111791300_B64","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/s41586-019-1650-0","article-title":"Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma","volume":"574","author":"Suzuki","year":"2019","journal-title":"Nature"},{"key":"2025102300111791300_B65","doi-asserted-by":"publisher","first-page":"2878","DOI":"10.1016\/j.cell.2021.04.012","article-title":"Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection","volume":"184","author":"Wan","year":"2021","journal-title":"Cell"},{"key":"2025102300111791300_B66","doi-asserted-by":"publisher","first-page":"5837","DOI":"10.1093\/nar\/gkr203","article-title":"Cryptic splice sites and split genes","volume":"39","author":"Kapustin","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B67","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/s41576-022-00556-8","article-title":"Regulation of pre-mRNA splicing: roles in physiology and disease, and therapeutic prospects","volume":"24","author":"Rogalska","year":"2023","journal-title":"Nat Rev Genet"},{"key":"2025102300111791300_B68","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41586-024-07019-6","article-title":"Genetic drivers of heterogeneity in type 2 diabetes pathophysiology","volume":"627","author":"Suzuki","year":"2024","journal-title":"Nature"},{"key":"2025102300111791300_B69","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.ajhg.2017.11.002","article-title":"The expanding landscape of alternative splicing variation in human populations","volume":"102","author":"Park","year":"2018","journal-title":"Am Hum Genet"},{"key":"2025102300111791300_B70","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/S0168-9525(01)02626-9","article-title":"Alternative splicing: multiple control mechanisms and involvement in human disease","volume":"18","author":"Caceres","year":"2002","journal-title":"Trends Genet"},{"key":"2025102300111791300_B71","doi-asserted-by":"publisher","first-page":"105630","DOI":"10.1016\/j.nbd.2022.105630","article-title":"Soluble TREM2: innocent bystander or active player in neurological diseases","volume":"165","author":"Filipello","year":"2022","journal-title":"Neurobiol Dis"},{"key":"2025102300111791300_B72","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41571-020-0350-x","article-title":"Roles and mechanisms of alternative splicing in cancer\u2014implications for care","volume":"17","author":"Bonnal","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"2025102300111791300_B73","doi-asserted-by":"crossref","first-page":"6671","DOI":"10.3390\/ijms21186671","article-title":"Relative and absolute quantification of aberrant and normal splice variants in HBB (IVSI-110 (G &gt;A)) beta-thalassemia","volume":"21","author":"Patsali","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025102300111791300_B74","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/s41586-023-06746-6","article-title":"Structural insights into intron catalysis and dynamics during splicing","volume":"624","author":"Xu","year":"2023","journal-title":"Nature"},{"key":"2025102300111791300_B75","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nrg2776","article-title":"Alternative splicing and evolution: diversification, exon definition and function","volume":"11","author":"Keren","year":"2010","journal-title":"Nat Rev Genet"},{"key":"2025102300111791300_B76","doi-asserted-by":"publisher","first-page":"4250","DOI":"10.1093\/nar\/gkm402","article-title":"Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization","volume":"35","author":"Buratti","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2025102300111791300_B77","doi-asserted-by":"publisher","first-page":"e854","DOI":"10.1002\/mgg3.854","article-title":"Activation of cryptic splice sites in three patients with chronic granulomatous disease","volume":"7","author":"de\u00a0Boer","year":"2019","journal-title":"Molec Gen & Gen Med"},{"key":"2025102300111791300_B78","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41586-022-04451-4","article-title":"Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers","volume":"603","author":"Kobayashi","year":"2022","journal-title":"Nature"},{"key":"2025102300111791300_B79","doi-asserted-by":"publisher","first-page":"eabg0879","DOI":"10.1126\/science.abg0879","article-title":"Structure of the activated human minor spliceosome","volume":"371","author":"Bai","year":"2021","journal-title":"Science"},{"key":"2025102300111791300_B80","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1126\/science.adn7272","article-title":"Structural basis of U12-type intron engagement by the fully assembled human minor spliceosome","volume":"383","author":"Bai","year":"2024","journal-title":"Science"},{"key":"2025102300111791300_B81","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev-biochem-013118-111024","article-title":"How Is precursor messenger RNA spliced by the spliceosome?","volume":"89","author":"Wan","year":"2020","journal-title":"Annu Rev Biochem"},{"key":"2025102300111791300_B82","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.molcel.2024.02.011","article-title":"Alternative splicing decouples local from global PRC2 activity","volume":"84","author":"Arecco","year":"2024","journal-title":"Mol Cell"},{"key":"2025102300111791300_B83","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.celrep.2016.08.096","article-title":"A high-density map for navigating the human polycomb complexome","volume":"17","author":"Hauri","year":"2016","journal-title":"Cell Rep"},{"key":"2025102300111791300_B84","doi-asserted-by":"publisher","first-page":"3885","DOI":"10.1016\/j.molcel.2024.08.025","article-title":"Activation of automethylated PRC2 by dimerization on chromatin","volume":"84","author":"Sauer","year":"2024","journal-title":"Mol Cell"},{"key":"2025102300111791300_B85","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/S0092-8674(02)00897-8","article-title":"Ras and Rap control AMPA receptor trafficking during synaptic plasticity","volume":"110","author":"Zhu","year":"2002","journal-title":"Cell"},{"key":"2025102300111791300_B86","doi-asserted-by":"publisher","first-page":"e30404","DOI":"10.1371\/journal.pone.0030404","article-title":"TLR signaling paralyzes monocyte chemotaxis through synergized effects of p38 MAPK and global Rap-1 activation","volume":"7","author":"Yi","year":"2012","journal-title":"PLoS One"},{"key":"2025102300111791300_B87","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1242\/jcs.114.6.1221","article-title":"Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase","volume":"114","author":"Sawada","year":"2001","journal-title":"J Cell Sci"},{"key":"2025102300111791300_B88","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.3390\/ijms18061172","article-title":"EZH2 in cancer progression and potential application in cancer therapy: a friend or foe?","volume":"18","author":"Yan","year":"2017","journal-title":"Int J Mol Sci"},{"key":"2025102300111791300_B89","doi-asserted-by":"publisher","first-page":"e2316","DOI":"10.1038\/cddis.2016.198","article-title":"DNA-PK-mediated phosphorylation of EZH2 regulates the DNA damage-induced apoptosis to maintain T-cell genomic integrity","volume":"7","author":"Wang","year":"2016","journal-title":"Cell Death Dis"},{"key":"2025102300111791300_B90","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1097\/FJC.0000000000001062","article-title":"EZH2 as an epigenetic regulator of cardiovascular development and diseases","volume":"78","author":"Yuan","year":"2021","journal-title":"J Cardiovasc Pharmacol"},{"key":"2025102300111791300_B91","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1093\/cvr\/cvu023","article-title":"Inhibitors of suppressive histone modification promote direct reprogramming of fibroblasts to cardiomyocyte-like cells","volume":"102","author":"Hirai","year":"2014","journal-title":"Cardiovasc Res"},{"key":"2025102300111791300_B92","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/j.celrep.2019.06.065","article-title":"PDGFR-beta signaling regulates cardiomyocyte proliferation and myocardial regeneration","volume":"28","author":"Yue","year":"2019","journal-title":"Cell Rep"},{"key":"2025102300111791300_B93","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s13045-020-00937-8","article-title":"EZH2: a novel target for cancer treatment","volume":"13","author":"Duan","year":"2020","journal-title":"J Hematol Oncol"},{"key":"2025102300111791300_B94","doi-asserted-by":"publisher","first-page":"8617","DOI":"10.3390\/ijms21228617","article-title":"EZH2 as a potential target for NAFLD therapy","volume":"21","author":"Lim","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025102300111791300_B95","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1177\/1073858417747839","article-title":"Polycomb repressive complex 2: emerging roles in the central nervous system","volume":"24","author":"Liu","year":"2018","journal-title":"Neuroscientist"},{"key":"2025102300111791300_B96","doi-asserted-by":"publisher","first-page":"2663","DOI":"10.1101\/gad.225888.113","article-title":"Nucleosome-binding activities within JARID2 and EZH1 regulate the function of PRC2 on chromatin","volume":"27","author":"Son","year":"2013","journal-title":"Genes Dev"},{"key":"2025102300111791300_B97","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1101\/gad.1921610","article-title":"The JARID2\u2013PRC2 duality","volume":"24","author":"Herz","year":"2010","journal-title":"Genes Dev"},{"key":"2025102300111791300_B98","doi-asserted-by":"publisher","first-page":"5947","DOI":"10.1038\/s41467-020-19722-9","article-title":"Polycomb group-mediated histone H2A monoubiquitination in epigenome regulation and nuclear processes","volume":"11","author":"Barbour","year":"2020","journal-title":"Nat Commun"},{"key":"2025102300111791300_B99","doi-asserted-by":"publisher","first-page":"e4189","DOI":"10.7717\/peerj.4189","article-title":"Function of JARID2 in bovines during early embryonic development","volume":"5","author":"Fu","year":"2017","journal-title":"PeerJ"},{"key":"2025102300111791300_B100","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.tcb.2010.10.004","article-title":"Inactive yet indispensable: the tale of Jarid2","volume":"21","author":"Landeira","year":"2011","journal-title":"Trends Cell Biol"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/53\/17\/gkaf869\/64870028\/gkaf869.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/53\/17\/gkaf869\/64870028\/gkaf869.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T04:11:25Z","timestamp":1761192685000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/doi\/10.1093\/nar\/gkaf869\/8249849"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,5]]},"references-count":100,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2025,9,5]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaf869","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9,23]]},"published":{"date-parts":[[2025,9,5]]},"article-number":"gkaf869"}}