{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T22:26:47Z","timestamp":1777933607351,"version":"3.51.4"},"reference-count":57,"publisher":"SAGE Publications","issue":"19","license":[{"start":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T00:00:00Z","timestamp":1367971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>\n                    Epigenetic regulation is implicated in embryonic development and the control of gene expression in a cell-specific manner. However, little is known about the role of histone methylation changes on human cardiac differentiation and maturation. Using human embryonic stem cells (hESCs) and their derived ventricular (\n                    <jats:bold>V<\/jats:bold>\n                    ) cardiomyocytes (CMs) as a model, we examined trimethylation of histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) on promoters of genes associated with cardiac electrophysiology, contraction, and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling. To avoid ambiguities due to heterogeneous chamber-specific types, hESC-derived ventricular cardiomyocytes (\n                    <jats:bold>V<\/jats:bold>\n                    CMs) were selected by dual zeocin-GFP expression under the transcriptional control of the\n                    <jats:italic toggle=\"yes\">MLC2v<\/jats:italic>\n                    promoter and confirmed electrophysiologically by its signature action potential phenotype. High levels of H3K4me3 are present on pluripotency genes in hESCs with an absence of H3K27me3. Human ESC-\n                    <jats:bold>V<\/jats:bold>\n                    CMS, relative to hESCs, were characterized by a profound loss of H3K27me3 and an enrichment of H3K4me3 marks on cardiac-specific genes, including\n                    <jats:italic toggle=\"yes\">MYH6<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">MYH7<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">MYL2<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">cTNT<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">ANF<\/jats:italic>\n                    . Gene transcripts encoding key voltage-gated ion channels and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -handling proteins in hESC-\n                    <jats:bold>V<\/jats:bold>\n                    CMs were significantly increased, which could be attributed to a distinct pattern of differential H3K4me3 and H3K27me3 profiles. Treatment of hESC-\n                    <jats:bold>V<\/jats:bold>\n                    CMs with the histone deacetylase inhibitor valproic acid increased H3K4me3 on gene promoters, induced hypertrophic growth (as gauged by cell volume and capacitance), and augmented cardiac gene expression, but it did not affect electrophysiological properties of these cells. Hence, cardiac differentiation of hESCs involves a dynamic shift in histone methylation, which differentially affects\n                    <jats:bold>V<\/jats:bold>\n                    CM gene expression and function. We conclude that the epigenetic state of hESC-\n                    <jats:bold>V<\/jats:bold>\n                    CMs is dynamic and primed to promote growth and developmental maturation, but that proper environmental stimuli with chromatin remodeling will be required to synergistically trigger global CM maturation to a more adult-like phenotype.\n                  <\/jats:p>","DOI":"10.1089\/scd.2013.0125","type":"journal-article","created":{"date-parts":[[2013,5,8]],"date-time":"2013-05-08T17:19:46Z","timestamp":1368033586000},"page":"2678-2690","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":26,"title":["Epigenetic Regulation of the Electrophysiological Phenotype of Human Embryonic Stem Cell-Derived Ventricular Cardiomyocytes: Insights for Driven Maturation and Hypertrophic Growth"],"prefix":"10.1177","volume":"22","author":[{"given":"Maggie Zi Ying","family":"Chow","sequence":"first","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"The University of Hong Kong","place":["Hong Kong"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Geng","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi-Wing","family":"Kong","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"The University of Hong Kong","place":["Hong Kong"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Keung","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"The University of Hong Kong","place":["Hong Kong"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacky Chun-Kit","family":"Fung","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth R.","family":"Boheler","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"National Institutes of Health"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald A.","family":"Li","sequence":"additional","affiliation":[{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"The University of Hong Kong","place":["Hong Kong"]},{"name":"Icahn School of Medicine at Mount 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