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H3K27me3 Does Not Orchestrate the Expression of Lineage-Specific Markers in hESC-Derived Hepatocytes In Vitro

Authors :
Jolien Vanhove
Mariaelena Pistoni
Marc Welters
Kristel Eggermont
Veerle Vanslembrouck
Nicky Helsen
Ruben Boon
Mustapha Najimi
Etienne Sokal
Philippe Collas
J. Willem Voncken
Catherine M. Verfaillie
Source :
Stem Cell Reports, Vol 7, Iss 2, Pp 192-206 (2016)
Publication Year :
2016
Publisher :
Elsevier, 2016.

Abstract

Although pluripotent stem cells can be differentiated into the hepatocyte lineages, such cells retain an immature phenotype. As the chromatin state of regulatory regions controls spatiotemporal gene expression during development, we evaluated changes in epigenetic histone marks in lineage-specific genes throughout in vitro hepatocyte differentiation from human embryonic stem cells (hESCs). Active acetylation and methylation marks at promoters and enhancers correlated with progressive changes in gene expression. However, repression-associated H3K27me3 marks at these control regions showed an inverse correlation with gene repression during transition from hepatic endoderm to a hepatocyte-like state. Inhibitor of Enhancer of Zeste Homolog 2 (EZH2) reduced H3K27me3 decoration but did not improve hepatocyte maturation. Thus, H3K27me3 at regulatory regions does not regulate transcription and appears dispensable for hepatocyte lineage differentiation of hESCs in vitro.

Details

Language :
English
ISSN :
22136711
Volume :
7
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Stem Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.861824b218e473a89560f975a0b24c8
Document Type :
article
Full Text :
https://doi.org/10.1016/j.stemcr.2016.06.013