Histone deacetylase activity is required for embryonic stem cell differentiation.
Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3-Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3-Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene-specific remodeling of chromatin structure during in vitro differentiation. genesis 38:32-38, 2004.
Lee
Jeong-Heon
JH
Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Department of Pediatrics and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Hart
Suzanne R L
SR
Skalnik
David G
DG
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005326:Fetal Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D050814:Octamer Transcription Factor-3; D011401:Promoter Regions, Genetic / Q000235:genetics; D011496:Protein Methyltransferases; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D020825:T-Box Domain Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000098908:Brachyury Protein
D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005326:Fetal Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; D006877:Hydroxamic Acids; D050814:Octamer Transcription Factor-3; D011496:Protein Methyltransferases; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D000098908:Brachyury Protein; C494174:Pou5f1 protein, mouse; C012589:trichostatin A