title: Role of epigenetics in liver-specific gene transcription, hepatocyte differentiation and stem cell reprogrammation.
abstract: Controlling both growth and differentiation of stem cells and their differentiated somatic progeny is a challenge in numerous fields, from preclinical drug development to clinical therapy. Recently, new insights into the underlying molecular mechanisms have unveiled key regulatory roles of epigenetic marks driving cellular pluripotency, differentiation and self-renewal/proliferation. Indeed, the transcription of genes, governing cell-fate decisions during development and maintenance of a cell's differentiated status in adult life, critically depends on the chromatin accessibility of transcription factors to genomic regulatory and coding regions. In this review, we discuss the epigenetic control of (liver-specific) gene-transcription and the intricate interplay between chromatin modulation, including histone (de)acetylation and DNA (de)methylation, and liver-enriched transcription factors. Special attention is paid to their role in directing hepatic differentiation of primary hepatocytes and stem cells in vitro.
authors.affiliation: Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Sarah.Snykers@vub.ac.be
authors.forename: Sarah
authors.initials: S
authors.lastname: Snykers
authors.forename: Tom
authors.initials: T
authors.lastname: Henkens
authors.forename: Evelien
authors.initials: E
authors.lastname: De Rop
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.forename: Joanna
authors.initials: J
authors.lastname: Fraczek
authors.forename: Joery
authors.initials: J
authors.lastname: De Kock
authors.forename: Evi
authors.initials: E
authors.lastname: De Prins
authors.forename: Albert
authors.initials: A
authors.lastname: Geerts
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000502:physiology; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology; D044127:Epigenesis, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D039902:Multipotent Stem Cells / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic
chemical_list: D056572:Histone Deacetylase Inhibitors; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases