{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:41:26Z","timestamp":1787020886968,"version":"build-2736575974"},"reference-count":101,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["HD093383"],"award-info":[{"award-number":["HD093383"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"USDA","award":["2020-67015-30882"],"award-info":[{"award-number":["2020-67015-30882"]}]},{"name":"NSF","award":["164805"],"award-info":[{"award-number":["164805"]}]},{"name":"Georgia Partners in Regenerative Medicine"},{"name":"Nelson and Bennie Abell Professorship in Biology"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Epigenetics &amp; Chromatin"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Directed differentiation of mouse embryonic stem cells (mESCs) or induced pluripotent stem cells (iPSCs) provides powerful models to dissect the molecular mechanisms leading to the formation of specific cell lineages. Treatment with histone deacetylase inhibitors can significantly enhance the efficiency of directed differentiation. However, the mechanisms are not well understood. Here, we use CUT&amp;RUN in combination with ATAC-seq to determine changes in both histone modifications and genome-wide chromatin accessibility following valproic acid (VPA) exposure. VPA induced a significant increase in global histone H3 acetylation (H3K56ac), a core histone modification affecting nucleosome stability, as well as enrichment at loci associated with cytoskeletal organization and cellular morphogenesis. In addition, VPA altered the levels of linker histone H1 subtypes and the total histone H1\/nucleosome ratio indicative of initial differentiation events. Notably, ATAC-seq analysis revealed changes in chromatin accessibility of genes involved in regulation of CDK serine\/threonine kinase activity and DNA duplex unwinding. Importantly, changes in chromatin accessibility were evident at several key genomic loci, such as the pluripotency factor Lefty, cardiac muscle troponin Tnnt2, and the homeodomain factor Hopx, which play critical roles in cardiomyocyte differentiation. Massive parallel transcription factor (TF) footprinting also indicates an increased occupancy of TFs involved in differentiation toward mesoderm and endoderm lineages and a loss of footprints of POU5F1\/SOX2 pluripotency factors following VPA treatment. Our results provide the first genome-wide analysis of the chromatin landscape following VPA-induced differentiation in mESCs and provide new mechanistic insight into the intricate molecular processes that govern departure from pluripotency and early lineage commitment.<\/jats:p>","DOI":"10.1186\/s13072-021-00432-5","type":"journal-article","created":{"date-parts":[[2021,12,26]],"date-time":"2021-12-26T22:02:22Z","timestamp":1640556142000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Changes in chromatin accessibility landscape and histone H3 core acetylation during valproic acid-induced differentiation of embryonic stem cells"],"prefix":"10.1186","volume":"14","author":[{"given":"Claudia","family":"Baumann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-4113","authenticated-orcid":false,"given":"Rabindranath","family":"De La Fuente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"issue":"6648","key":"432_CR1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/38444","volume":"389","author":"K Luger","year":"1997","unstructured":"Luger K, et al. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature. 1997;389(6648):251\u201360.","journal-title":"Nature"},{"issue":"1","key":"432_CR2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s10577-005-1024-3","volume":"14","author":"CL Woodcock","year":"2006","unstructured":"Woodcock CL, Skoultchi AI, Fan Y. Role of linker histone in chromatin structure and function: H1 stoichiometry and nucleosome repeat length. Chromosome Res. 2006;14(1):17\u201325.","journal-title":"Chromosome Res"},{"issue":"3","key":"432_CR3","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.ceb.2012.03.003","volume":"24","author":"Q Bian","year":"2012","unstructured":"Bian Q, Belmont AS. Revisiting higher-order and large-scale chromatin organization. Curr Opin Cell Biol. 2012;24(3):359\u201366.","journal-title":"Curr Opin Cell Biol"},{"key":"432_CR4","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ceb.2013.10.002","volume":"26","author":"AS Belmont","year":"2014","unstructured":"Belmont AS. Large-scale chromatin organization: the good, the surprising, and the still perplexing. Curr Opin Cell Biol. 2014;26:69\u201378.","journal-title":"Curr Opin Cell Biol"},{"issue":"1","key":"432_CR5","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.devcel.2005.10.017","volume":"10","author":"E Meshorer","year":"2006","unstructured":"Meshorer E, et al. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell. 2006;10(1):105\u201316.","journal-title":"Dev Cell"},{"issue":"5","key":"432_CR6","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.stem.2008.03.021","volume":"2","author":"S Efroni","year":"2008","unstructured":"Efroni S, et al. Global transcription in pluripotent embryonic stem cells. Cell Stem Cell. 2008;2(5):437\u201347.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"432_CR7","first-page":"245","volume":"48","author":"S Melcer","year":"2010","unstructured":"Melcer S, Meshorer E. Chromatin plasticity in pluripotent cells. Essays Biochem. 2010;48(1):245\u201362.","journal-title":"Essays Biochem"},{"issue":"4","key":"432_CR8","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2007.02.005","volume":"128","author":"T Kouzarides","year":"2007","unstructured":"Kouzarides T. Chromatin modifications and their function. Cell. 2007;128(4):693\u2013705.","journal-title":"Cell"},{"issue":"16","key":"432_CR9","doi-asserted-by":"publisher","first-page":"5941","DOI":"10.3390\/ijms21165941","volume":"21","author":"M Andr\u00e9s","year":"2020","unstructured":"Andr\u00e9s M, et al. Histone H1 post-translational modifications: update and future perspectives. Int J Mol Sci. 2020;21(16):5941.","journal-title":"Int J Mol Sci"},{"issue":"8","key":"432_CR10","first-page":"779","volume":"7","author":"P Norio","year":"2006","unstructured":"Norio P. DNA replication: the unbearable lightness of origins. 2006;7(8):779\u201381.","journal-title":"DNA replication: the unbearable lightness of origins"},{"issue":"21","key":"432_CR11","first-page":"10017","volume":"44","author":"WP Roos","year":"2016","unstructured":"Roos WP, Krumm A. The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair. Nucleic Acids Res. 2016;44(21):10017\u201330.","journal-title":"Nucleic Acids Res"},{"issue":"7530","key":"432_CR12","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nature13714","volume":"516","author":"TJ Stasevich","year":"2014","unstructured":"Stasevich TJ, et al. Regulation of RNA polymerase II activation by histone acetylation in single living cells. Nature. 2014;516(7530):272\u20135.","journal-title":"Nature"},{"issue":"3","key":"432_CR13","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/ng843","volume":"30","author":"C Maison","year":"2002","unstructured":"Maison C, et al. Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component. Nat Genet. 2002;30(3):329\u201334.","journal-title":"Nat Genet"},{"issue":"11","key":"432_CR14","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nrg.2016.112","volume":"17","author":"B Bonev","year":"2016","unstructured":"Bonev B, Cavalli G. Organization and function of the 3D genome. Nat Rev Genet. 2016;17(11):661\u201378.","journal-title":"Nat Rev Genet"},{"issue":"1","key":"432_CR15","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1146\/annurev.biochem.76.052705.162114","volume":"76","author":"MD Shahbazian","year":"2007","unstructured":"Shahbazian MD, Grunstein M. Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem. 2007;76(1):75\u2013100.","journal-title":"Annu Rev Biochem"},{"issue":"1","key":"432_CR16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.ccr.2012.06.008","volume":"22","author":"JS You","year":"2012","unstructured":"You JS, Jones PA. Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell. 2012;22(1):9\u201320.","journal-title":"Cancer Cell"},{"key":"432_CR17","doi-asserted-by":"crossref","unstructured":"Li, Y. and E. Seto, HDACs and HDAC Inhibitors in Cancer Development and Therapy. 2016. 6(10).","DOI":"10.1101\/cshperspect.a026831"},{"issue":"5","key":"432_CR18","doi-asserted-by":"publisher","first-page":"556","DOI":"10.3390\/genes11050556","volume":"11","author":"G Milazzo","year":"2020","unstructured":"Milazzo G, et al. Histone deacetylases (HDACs): evolution, specificity, role in transcriptional complexes, and pharmacological actionability. Genes. 2020;11(5):556.","journal-title":"Genes"},{"issue":"3","key":"432_CR19","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.3390\/molecules20033898","volume":"20","author":"M Mottamal","year":"2015","unstructured":"Mottamal M, et al. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015;20(3):3898\u2013941.","journal-title":"Molecules"},{"issue":"7","key":"432_CR20","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/nbt1418","volume":"26","author":"D Huangfu","year":"2008","unstructured":"Huangfu D, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol. 2008;26(7):795\u20137.","journal-title":"Nat Biotechnol"},{"issue":"4","key":"432_CR21","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.stem.2011.03.001","volume":"8","author":"F Anokye-Danso","year":"2011","unstructured":"Anokye-Danso F, et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell. 2011;8(4):376\u201388.","journal-title":"Cell Stem Cell"},{"issue":"8","key":"432_CR22","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1101\/gad.214023.113","volume":"27","author":"A Mottis","year":"2013","unstructured":"Mottis A, Mouchiroud L, Auwerx J. Emerging roles of the corepressors NCoR1 and SMRT in homeostasis. Genes Dev. 2013;27(8):819\u201335.","journal-title":"Genes Dev."},{"issue":"4","key":"432_CR23","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/s41556-018-0047-x","volume":"20","author":"Q Zhuang","year":"2018","unstructured":"Zhuang Q, et al. NCoR\/SMRT co-repressors cooperate with c-MYC to create an epigenetic barrier to somatic cell reprogramming. Nat Cell Biol. 2018;20(4):400\u201312.","journal-title":"Nat Cell Biol"},{"issue":"4","key":"432_CR24","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.stem.2018.03.005","volume":"22","author":"S Cao","year":"2018","unstructured":"Cao S, et al. Chromatin accessibility dynamics during chemical induction of pluripotency. Cell Stem Cell. 2018;22(4):529-542.e5.","journal-title":"Cell Stem Cell"},{"issue":"1","key":"432_CR25","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41589-020-0618-6","volume":"17","author":"K-P Kim","year":"2021","unstructured":"Kim K-P, et al. Permissive epigenomes endow reprogramming competence to transcriptional regulators. Nat Chem Biol. 2021;17(1):47\u201356.","journal-title":"Nat Chem Biol"},{"issue":"2","key":"432_CR26","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1128\/MCB.00631-13","volume":"34","author":"F Yin","year":"2014","unstructured":"Yin F, et al. LSD1 regulates pluripotency of embryonic stem\/carcinoma cells through histone deacetylase 1-mediated deacetylation of histone H4 at lysine 16. Mol Cell Biol. 2014;34(2):158\u201379.","journal-title":"Mol Cell Biol"},{"issue":"1","key":"432_CR27","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s00441-019-03027-5","volume":"378","author":"H Najafipour","year":"2019","unstructured":"Najafipour H, et al. The effect of sodium valproate on differentiation of human adipose-derived stem cells into cardiomyocyte-like cells in two-dimensional culture and fibrin scaffold conditions. Cell Tissue Res. 2019;378(1):127\u201341.","journal-title":"Cell Tissue Res"},{"key":"432_CR28","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.biomaterials.2015.07.063","volume":"70","author":"C Morez","year":"2015","unstructured":"Morez C, et al. Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues. Biomaterials. 2015;70:94\u2013104.","journal-title":"Biomaterials"},{"issue":"S1","key":"432_CR29","first-page":"71","volume":"60","author":"S Stejskal","year":"2014","unstructured":"Stejskal S, Tesarov\u00e1 L, Koutn\u00e1 I. Mysterious role of H3K56ac in embryonic stem cells. Folia Biol. 2014;60(S1):71\u20135.","journal-title":"Folia Biol"},{"key":"432_CR30","doi-asserted-by":"publisher","first-page":"10152","DOI":"10.1038\/ncomms10152","volume":"6","author":"M Bernier","year":"2015","unstructured":"Bernier M, et al. Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics. Nat Commun. 2015;6:10152.","journal-title":"Nat Commun"},{"key":"432_CR31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.mrfmmm.2015.01.005","volume":"776","author":"Q Zhu","year":"2015","unstructured":"Zhu Q, et al. Damaged DNA-binding protein down-regulates epigenetic mark H3K56Ac through histone deacetylase 1 and 2. Mutat Res. 2015;776:16\u201323.","journal-title":"Mutat Res"},{"issue":"38","key":"432_CR32","doi-asserted-by":"publisher","first-page":"13805","DOI":"10.1073\/pnas.1415330111","volume":"111","author":"S Musah","year":"2014","unstructured":"Musah S, et al. Substratum-induced differentiation of human pluripotent stem cells reveals the coactivator YAP is a potent regulator of neuronal specification. Proc Natl Acad Sci USA. 2014;111(38):13805\u201310.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"432_CR33","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1089\/adt.2015.655","volume":"13","author":"O Sirenko","year":"2015","unstructured":"Sirenko O, et al. High-content assays for characterizing the viability and morphology of 3D cancer spheroid cultures. Assay Drug Dev Technol. 2015;13(7):402\u201314.","journal-title":"Assay Drug Dev Technol"},{"issue":"11","key":"432_CR34","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/nrm3890","volume":"15","author":"P Tessarz","year":"2014","unstructured":"Tessarz P, Kouzarides T. Histone core modifications regulating nucleosome structure and dynamics. Nat Rev Mol Cell Biol. 2014;15(11):703\u20138.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"18","key":"432_CR35","doi-asserted-by":"publisher","first-page":"8242","DOI":"10.1073\/pnas.1000478107","volume":"107","author":"OM Dovey","year":"2010","unstructured":"Dovey OM, Foster CT, Cowley SM. Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci USA. 2010;107(18):8242\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"432_CR36","doi-asserted-by":"publisher","first-page":"e10531","DOI":"10.1371\/journal.pone.0010531","volume":"5","author":"K Ahmed","year":"2010","unstructured":"Ahmed K, et al. Global chromatin architecture reflects pluripotency and lineage commitment in the early mouse embryo. PLoS ONE. 2010;5(5):e10531.","journal-title":"PLoS ONE"},{"key":"432_CR37","doi-asserted-by":"crossref","unstructured":"Zhang, Y., et al., Histone h1 depletion impairs embryonic stem cell differentiation. PLoS Genet, 2012. 8(5): p. e1002691.","DOI":"10.1371\/journal.pgen.1002691"},{"issue":"3","key":"432_CR38","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.bbagrm.2015.12.002","volume":"1859","author":"C Pan","year":"2016","unstructured":"Pan C, Fan Y. Role of H1 linker histones in mammalian development and stem cell differentiation. Biochim Biophys Acta. 2016;1859(3):496\u2013509.","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"432_CR39","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/nsmb.2581","volume":"20","author":"P Tropberger","year":"2013","unstructured":"Tropberger P, Schneider R. Scratching the (lateral) surface of chromatin regulation by histone modifications. Nat Struct Mol Biol. 2013;20(6):657\u201361.","journal-title":"Nat Struct Mol Biol"},{"issue":"22","key":"432_CR40","doi-asserted-by":"publisher","first-page":"10060","DOI":"10.1128\/MCB.25.22.10060-10070.2005","volume":"25","author":"EM Hyland","year":"2005","unstructured":"Hyland EM, et al. Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol Cell Biol. 2005;25(22):10060\u201370.","journal-title":"Mol Cell Biol"},{"issue":"5","key":"432_CR41","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1016\/j.bpj.2010.06.046","volume":"99","author":"AT Fenley","year":"2010","unstructured":"Fenley AT, Adams DA, Onufriev AV. Charge state of the globular histone core controls stability of the nucleosome. Biophys J. 2010;99(5):1577\u201385.","journal-title":"Biophys J"},{"key":"432_CR42","doi-asserted-by":"crossref","unstructured":"Dilg, D., et al., HIRA Is Required for Heart Development and Directly Regulates Tnni2 and Tnnt3. PLoS One, 2016. 11(8): p. e0161096.","DOI":"10.1371\/journal.pone.0161096"},{"issue":"4","key":"432_CR43","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1111\/dgd.12659","volume":"62","author":"Y Meng","year":"2020","unstructured":"Meng Y, et al. Polycomb group RING finger protein 5 influences several developmental signaling pathways during the in vitro differentiation of mouse embryonic stem cells. Dev Growth Differ. 2020;62(4):232\u201342.","journal-title":"Dev Growth Differ"},{"issue":"1","key":"432_CR44","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1161\/CIRCRESAHA.116.304472","volume":"116","author":"J Li","year":"2015","unstructured":"Li J, et al. Alpha-catenins control cardiomyocyte proliferation by regulating Yap activity. Circ Res. 2015;116(1):70\u20139.","journal-title":"Circ Res"},{"issue":"5","key":"432_CR45","doi-asserted-by":"publisher","first-page":"dev149823","DOI":"10.1242\/dev.149823","volume":"145","author":"A Vite","year":"2018","unstructured":"Vite A, et al. \u03b1-Catenin-dependent cytoskeletal tension controls Yap activity in the heart. Development. 2018;145(5):dev149823.","journal-title":"Development"},{"key":"432_CR46","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3389\/fphar.2016.00142","volume":"7","author":"S Sasagawa","year":"2016","unstructured":"Sasagawa S, et al. Comparative transcriptome analysis identifies CCDC80 as a novel gene associated with pulmonary arterial hypertension. Front Pharmacol. 2016;7:142.","journal-title":"Front Pharmacol"},{"issue":"4","key":"432_CR47","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s00438-020-01666-w","volume":"295","author":"A Pozarickij","year":"2020","unstructured":"Pozarickij A, Williams C, Guggenheim JA. Non-additive (dominance) effects of genetic variants associated with refractive error and myopia. Mol Genet Genomics. 2020;295(4):843\u201353.","journal-title":"Mol Genet Genomics"},{"issue":"4","key":"432_CR48","doi-asserted-by":"publisher","first-page":"295","DOI":"10.4149\/gpb_2019018","volume":"38","author":"J Liang","year":"2019","unstructured":"Liang J, Liu N, Xin H. Knockdown long non-coding RNA PEG10 inhibits proliferation, migration and invasion of glioma cell line U251 by regulating miR-506. Gen Physiol Biophys. 2019;38(4):295\u2013304.","journal-title":"Gen Physiol Biophys"},{"issue":"3","key":"432_CR49","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.devcel.2010.08.012","volume":"19","author":"CM Trivedi","year":"2010","unstructured":"Trivedi CM, et al. Hopx and Hdac2 interact to modulate Gata4 acetylation and embryonic cardiac myocyte proliferation. Dev Cell. 2010;19(3):450\u20139.","journal-title":"Dev Cell"},{"issue":"2","key":"432_CR50","first-page":"L191","volume":"291","author":"Z Yin","year":"2006","unstructured":"Yin Z, et al. Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression. Am J Physiol. 2006; 291(2): L191\u2013L199.","journal-title":"Am J Physiol"},{"issue":"1","key":"432_CR51","doi-asserted-by":"publisher","first-page":"4267","DOI":"10.1038\/s41467-020-18035-1","volume":"11","author":"M Bentsen","year":"2020","unstructured":"Bentsen M, et al. ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation. Nat Commun. 2020;11(1):4267.","journal-title":"Nat Commun"},{"issue":"1","key":"432_CR52","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1093\/abbs\/gmx120","volume":"50","author":"C Liu","year":"2018","unstructured":"Liu C, Peng G, Jing N. TGF-\u03b2 signaling pathway in early mouse development and embryonic stem cells. Acta Biochim Biophys Sin. 2018;50(1):68\u201373.","journal-title":"Acta Biochim Biophys Sin"},{"issue":"4","key":"432_CR53","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.molcel.2009.02.004","volume":"33","author":"W Xie","year":"2009","unstructured":"Xie W, et al. Histone h3 lysine 56 acetylation is linked to the core transcriptional network in human embryonic stem cells. Mol Cell. 2009;33(4):417\u201327.","journal-title":"Mol Cell"},{"issue":"28","key":"432_CR54","doi-asserted-by":"publisher","first-page":"11493","DOI":"10.1073\/pnas.1309914110","volume":"110","author":"Y Tan","year":"2013","unstructured":"Tan Y, et al. Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency. Proc Natl Acad Sci USA. 2013;110(28):11493\u20138.","journal-title":"Proc Natl Acad Sci USA"},{"key":"432_CR55","doi-asserted-by":"publisher","first-page":"e21856","DOI":"10.7554\/eLife.21856","volume":"6","author":"PJ Skene","year":"2017","unstructured":"Skene PJ, Henikoff S. An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites. Elife. 2017;6:e21856.","journal-title":"Elife"},{"issue":"1","key":"432_CR56","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1038\/s41467-019-09624-w","volume":"10","author":"E Lavarone","year":"2019","unstructured":"Lavarone E, Barbieri CM, Pasini D. Dissecting the role of H3K27 acetylation and methylation in PRC2 mediated control of cellular identity. Nat Commun. 2019;10(1):1679.","journal-title":"Nat Commun"},{"issue":"1","key":"432_CR57","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.celrep.2013.09.003","volume":"5","author":"L Li","year":"2013","unstructured":"Li L, et al. Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep. 2013;5(1):3\u201312.","journal-title":"Cell Rep"},{"issue":"1","key":"432_CR58","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s12915-019-0677-x","volume":"17","author":"E Rodr\u00edguez-Carballo","year":"2019","unstructured":"Rodr\u00edguez-Carballo E, et al. Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes. BMC Biol. 2019;17(1):55.","journal-title":"BMC Biol"},{"issue":"1","key":"432_CR59","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13072-019-0287-4","volume":"12","author":"MP Meers","year":"2019","unstructured":"Meers MP, Tenenbaum D, Henikoff S. Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling. Epigenet Chromatin. 2019;12(1):42.","journal-title":"Epigenet Chromatin"},{"key":"432_CR60","doi-asserted-by":"crossref","unstructured":"Yang J.-H, et al., Erosion of the epigenetic landscape and loss of cellular identity as a cause of aging in mammals. bioRxiv, 2019: p. 808642.","DOI":"10.2139\/ssrn.3461780"},{"issue":"1","key":"432_CR61","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.stem.2010.04.017","volume":"7","author":"X Zhang","year":"2010","unstructured":"Zhang X, et al. Pax6 is a human neuroectoderm cell fate determinant. Cell Stem Cell. 2010;7(1):90\u2013100.","journal-title":"Cell Stem Cell"},{"issue":"6198","key":"432_CR62","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1126\/science.1254745","volume":"345","author":"E Gonzalez-Mu\u00f1oz","year":"2014","unstructured":"Gonzalez-Mu\u00f1oz E, et al. Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming. Science. 2014;345(6198):822\u20135.","journal-title":"Science"},{"issue":"5","key":"432_CR63","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1089\/scd.2013.0220","volume":"23","author":"D-K Kim","year":"2014","unstructured":"Kim D-K, et al. Lefty1 and lefty2 control the balance between self-renewal and pluripotent differentiation of mouse embryonic stem cells. Stem Cells Dev. 2014;23(5):457\u201366.","journal-title":"Stem Cells Dev"},{"issue":"9","key":"432_CR64","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1634\/stemcells.2006-0075","volume":"24","author":"S Tabibzadeh","year":"2006","unstructured":"Tabibzadeh S, Hemmati-Brivanlou A. Lefty at the crossroads of \u201cStemness\u201d and Differentiative events. Stem Cells. 2006;24(9):1998\u20132006.","journal-title":"Stem Cells."},{"issue":"4","key":"432_CR65","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1101\/gr.272468.120","volume":"31","author":"G Singh","year":"2021","unstructured":"Singh G, et al. A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells. Genome Res. 2021;31(4):564\u201375.","journal-title":"Genome Res"},{"issue":"7391","key":"432_CR66","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/nature10953","volume":"483","author":"TT Onder","year":"2012","unstructured":"Onder TT, et al. Chromatin-modifying enzymes as modulators of reprogramming. Nature. 2012;483(7391):598\u2013602.","journal-title":"Nature"},{"issue":"6","key":"432_CR67","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1016\/j.celrep.2016.10.011","volume":"17","author":"NC Gomez","year":"2016","unstructured":"Gomez NC, et al. Widespread chromatin accessibility at repetitive elements links stem cells with human cancer. Cell Rep. 2016;17(6):1607\u201320.","journal-title":"Cell Rep"},{"issue":"12","key":"432_CR68","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/nmat3777","volume":"12","author":"TL Downing","year":"2013","unstructured":"Downing TL, et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat Mater. 2013;12(12):1154\u201362.","journal-title":"Nat Mater"},{"issue":"11","key":"432_CR69","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1038\/cdd.2017.108","volume":"24","author":"S Segura-Bayona","year":"2017","unstructured":"Segura-Bayona S, et al. Differential requirements for Tousled-like kinases 1 and 2 in mammalian development. Cell Death Differ. 2017;24(11):1872\u201385.","journal-title":"Cell Death Differ"},{"issue":"13","key":"432_CR70","doi-asserted-by":"publisher","first-page":"4559","DOI":"10.1128\/MCB.23.13.4559-4572.2003","volume":"23","author":"Y Fan","year":"2003","unstructured":"Fan Y, et al. H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo. Mol Cell Biol. 2003;23(13):4559\u201372.","journal-title":"Mol Cell Biol"},{"issue":"4","key":"432_CR71","doi-asserted-by":"publisher","first-page":"2440","DOI":"10.1074\/jbc.274.4.2440","volume":"274","author":"A Verdel","year":"1999","unstructured":"Verdel A, Khochbin S. Identification of a new family of higher eukaryotic histone deacetylases: coordinate expression of differentiation-dependent chromatin modifiers*. J Biol Chem. 1999;274(4):2440\u20135.","journal-title":"J Biol Chem"},{"key":"432_CR72","doi-asserted-by":"crossref","unstructured":"Kress, H., R. T\u00f6njes, and D. Doenecke, Butyrate induced accumulation of a 2.3 kb polyadenylated H1(0) histone mRNA in HeLa cells. Nucleic Acids Res, 1986. 14(18): p. 7189\u201397.","DOI":"10.1093\/nar\/14.18.7189"},{"issue":"2","key":"432_CR73","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0378-1119(93)90560-P","volume":"128","author":"S Khochbin","year":"1993","unstructured":"Khochbin S, Wolffe AP. Developmental regulation and butyrate-inducible transcription of the Xenopus histone H1(0) promoter. Gene. 1993;128(2):173\u201380.","journal-title":"Gene"},{"issue":"3","key":"432_CR74","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1111\/j.1432-1033.1994.00885.x","volume":"224","author":"V Girardot","year":"1994","unstructured":"Girardot V, et al. Relationship between core histone acetylation and histone H1(0) gene activity. Eur J Biochem. 1994;224(3):885\u201392.","journal-title":"Eur J Biochem"},{"issue":"2","key":"432_CR75","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.bbrc.2007.08.120","volume":"363","author":"J Rao","year":"2007","unstructured":"Rao J, et al. Trichostatin-A induces differential changes in histone protein dynamics and expression in HeLa cells. Biochem Biophys Res Commun. 2007;363(2):263\u20138.","journal-title":"Biochem Biophys Res Commun"},{"key":"432_CR76","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.ijbiomac.2017.02.098","volume":"99","author":"J Sargolzaei","year":"2017","unstructured":"Sargolzaei J, et al. Spectroscopic analysis of the interaction of valproic acid with histone H1 in solution and in chromatin structure. Int J Biol Macromol. 2017;99:427\u201332.","journal-title":"Int J Biol Macromol"},{"key":"432_CR77","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ijbiomac.2020.06.265","volume":"163","author":"B de Campos Vidal","year":"2020","unstructured":"de Campos Vidal B, Mello MLS. Sodium valproate (VPA) interactions with DNA and histones. Int J Biol Macromol. 2020;163:219\u201331.","journal-title":"Int J Biol Macromol"},{"issue":"2","key":"432_CR78","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.cell.2011.03.003","volume":"145","author":"YS Ang","year":"2011","unstructured":"Ang YS, et al. Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network. Cell. 2011;145(2):183\u201397.","journal-title":"Cell"},{"key":"432_CR79","doi-asserted-by":"publisher","first-page":"276","DOI":"10.2741\/2678","volume":"13","author":"M Zhan","year":"2008","unstructured":"Zhan M. Genomic studies to explore self-renewal and differentiation properties of embryonic stem cells. Front Biosci. 2008;13:276\u201383.","journal-title":"Front Biosci"},{"issue":"6","key":"432_CR80","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1002\/stem.59","volume":"27","author":"A Golebiewska","year":"2009","unstructured":"Golebiewska A, et al. Epigenetic landscaping during hESC differentiation to neural cells. Stem Cells. 2009;27(6):1298\u2013308.","journal-title":"Stem Cells"},{"issue":"14","key":"432_CR81","doi-asserted-by":"publisher","first-page":"e1900047","DOI":"10.1002\/pmic.201900047","volume":"19","author":"G van Mierlo","year":"2019","unstructured":"van Mierlo G, Wester RA, Marks H. A Mass spectrometry survey of chromatin-associated proteins in pluripotency and early lineage commitment. Proteomics. 2019;19(14):e1900047.","journal-title":"Proteomics"},{"issue":"10","key":"432_CR82","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.7150\/ijbs.7998","volume":"9","author":"DC Kraushaar","year":"2013","unstructured":"Kraushaar DC, Zhao K. The epigenomics of embryonic stem cell differentiation. Int J Biol Sci. 2013;9(10):1134\u201344.","journal-title":"Int J Biol Sci"},{"issue":"17","key":"432_CR83","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1101\/gad.303321.117","volume":"31","author":"L Xie","year":"2017","unstructured":"Xie L, et al. A dynamic interplay of enhancer elements regulates Klf4 expression in na\u00efve pluripotency. Genes Dev. 2017;31(17):1795\u2013808.","journal-title":"Genes Dev"},{"issue":"9","key":"432_CR84","doi-asserted-by":"publisher","first-page":"2280","DOI":"10.1016\/j.bpj.2019.12.038","volume":"118","author":"J Huertas","year":"2020","unstructured":"Huertas J, et al. Nucleosomal DNA dynamics mediate Oct4 pioneer factor binding. Biophys J. 2020;118(9):2280\u201396.","journal-title":"Biophys J"},{"issue":"6","key":"432_CR85","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1016\/j.yjmcc.2011.02.015","volume":"50","author":"CM Trivedi","year":"2011","unstructured":"Trivedi CM, et al. Homeodomain only Protein X is down-regulated in human heart failure. J Mol Cell Cardiol. 2011;50(6):1056\u20138.","journal-title":"J Mol Cell Cardiol"},{"issue":"13","key":"432_CR86","doi-asserted-by":"publisher","first-page":"3411","DOI":"10.1093\/emboj\/cdg315","volume":"22","author":"OH Kr\u00e4mer","year":"2003","unstructured":"Kr\u00e4mer OH, et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J. 2003;22(13):3411\u201320.","journal-title":"EMBO J."},{"issue":"39","key":"432_CR87","doi-asserted-by":"publisher","first-page":"36734","DOI":"10.1074\/jbc.M101287200","volume":"276","author":"CJ Phiel","year":"2001","unstructured":"Phiel CJ, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001;276(39):36734\u201341.","journal-title":"J Biol Chem"},{"issue":"4","key":"432_CR88","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.stem.2018.09.009","volume":"23","author":"CE Friedman","year":"2018","unstructured":"Friedman CE, et al. Single-cell transcriptomic analysis of cardiac differentiation from human PSCs reveals HOPX-dependent cardiomyocyte maturation. Cell Stem Cell. 2018;23(4):586-598.e8.","journal-title":"Cell Stem Cell"},{"issue":"6561","key":"432_CR89","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/379131a0","volume":"379","author":"GD Penny","year":"1996","unstructured":"Penny GD, et al. Requirement for Xist in X chromosome inactivation. Nature. 1996;379(6561):131\u20137.","journal-title":"Nature"},{"key":"432_CR90","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/S0076-6879(03)77005-0","volume":"377","author":"Y Fan","year":"2004","unstructured":"Fan Y, Skoultchi AI. Genetic analysis of H1 linker histone subtypes and their functions in mice. Methods Enzymol. 2004;377:85\u2013107.","journal-title":"Methods Enzymol"},{"issue":"12","key":"432_CR91","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro JD, et al. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10(12):1213\u20138.","journal-title":"Nat Methods"},{"issue":"9","key":"432_CR92","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang Y, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9(9):R137.","journal-title":"Genome Biol"},{"key":"432_CR93","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3389\/fgene.2018.00250","volume":"9","author":"M Divate","year":"2018","unstructured":"Divate M, Cheung E. GUAVA: a graphical user interface for the analysis and visualization of ATAC-seq data. Front Genet. 2018;9:250.","journal-title":"Front Genet"},{"issue":"12","key":"432_CR94","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.","journal-title":"Genome Biol"},{"issue":"D1","key":"432_CR95","first-page":"D87","volume":"48","author":"O Fornes","year":"2020","unstructured":"Fornes O, et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2020;48(D1):D87-d92.","journal-title":"Nucleic Acids Res"},{"issue":"Database issue","key":"432_CR96","doi-asserted-by":"publisher","first-page":"D493","DOI":"10.1093\/nar\/gkh103","volume":"32","author":"D Karolchik","year":"2004","unstructured":"Karolchik D, et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res. 2004;32(Database issue):D493-6.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"432_CR97","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012;9(4):357\u20139.","journal-title":"Nat Methods"},{"issue":"D1","key":"432_CR98","first-page":"D682","volume":"48","author":"AD Yates","year":"2020","unstructured":"Yates AD, et al. Ensembl 2020. Nucleic Acids Res. 2020;48(D1):D682-d688.","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"432_CR99","doi-asserted-by":"publisher","first-page":"4486","DOI":"10.1038\/s41467-020-18009-3","volume":"11","author":"C Baumann","year":"2020","unstructured":"Baumann C, et al. Helicase LSH\/Hells regulates kinetochore function, histone H3\/Thr3 phosphorylation and centromere transcription during oocyte meiosis. Nat Commun. 2020;11(1):4486.","journal-title":"Nat Commun"},{"key":"432_CR100","doi-asserted-by":"publisher","first-page":"6546","DOI":"10.1038\/ncomms7546","volume":"6","author":"SJ Yoon","year":"2015","unstructured":"Yoon SJ, Foley JW, Baker JC. HEB associates with PRC2 and SMAD2\/3 to regulate developmental fates. Nat Commun. 2015;6:6546.","journal-title":"Nat Commun"},{"issue":"5","key":"432_CR101","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/nprot.2018.015","volume":"13","author":"PJ Skene","year":"2018","unstructured":"Skene PJ, Henikoff JG, Henikoff S. Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Nat Protoc. 2018;13(5):1006\u201319.","journal-title":"Nat Protoc"}],"container-title":["Epigenetics &amp; Chromatin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13072-021-00432-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13072-021-00432-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13072-021-00432-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T04:08:22Z","timestamp":1676088502000},"score":1,"resource":{"primary":{"URL":"https:\/\/epigeneticsandchromatin.biomedcentral.com\/articles\/10.1186\/s13072-021-00432-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,27]]},"references-count":101,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["432"],"URL":"https:\/\/doi.org\/10.1186\/s13072-021-00432-5","relation":{},"ISSN":["1756-8935"],"issn-type":[{"value":"1756-8935","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,27]]},"assertion":[{"value":"17 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare no competing financial interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"58"}}