Role of epigenetics in liver-specific gene transcription, hepatocyte differentiation and stem cell reprogrammation.
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.
Snykers
Sarah
S
Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Sarah.Snykers@vub.ac.be
Henkens
Tom
T
De Rop
Evelien
E
Vinken
Mathieu
M
Fraczek
Joanna
J
De Kock
Joery
J
De Prins
Evi
E
Geerts
Albert
A
Rogiers
Vera
V
Vanhaecke
Tamara
T
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
D056572:Histone Deacetylase Inhibitors; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D006655:Histone Deacetylases