title: H3K27me3 Does Not Orchestrate the Expression of Lineage-Specific Markers in hESC-Derived Hepatocytes In Vitro.
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.
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium. Electronic address: jolien.vanhove@med.kuleuven.be.
authors.forename: Jolien
authors.initials: J
authors.lastname: Vanhove
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium. Electronic address: mariaelena.pistoni@gmail.com.
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Pistoni
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Welters
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Eggermont
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanslembrouck
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Nicky
authors.initials: N
authors.lastname: Helsen
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Ruben
authors.initials: R
authors.lastname: Boon
authors.affiliation: Laboratory of Pediatric Hepatology and Cell Therapy, Université Catholique de Louvain, Cliniques St-Luc - Institut de Recherche Expérimentale et Clinique (IREC), Brussels 1200, Belgium.
authors.forename: Mustapha
authors.initials: M
authors.lastname: Najimi
authors.affiliation: Laboratory of Pediatric Hepatology and Cell Therapy, Université Catholique de Louvain, Cliniques St-Luc - Institut de Recherche Expérimentale et Clinique (IREC), Brussels 1200, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Faculty of Medicine, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo 0372, Norway.
authors.forename: Philippe
authors.initials: P
authors.lastname: Collas
authors.affiliation: Department of Molecular Genetics, Maastricht University Medical Centre, 6229 ER Maastricht, the Netherlands.
authors.forename: J Willem
authors.initials: JW
authors.lastname: Voncken
authors.affiliation: Department Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven 3000, Belgium.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D015415:Biomarkers; D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D008239:Lysine; D004121:Dimethyl Sulfoxide