Abstract
Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells, where it has been shown to be important for maintaining pluripotency. Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 re-expression, thereby preventing reprogramming.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation / drug effects
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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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Chromobox Protein Homolog 5
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Chromosomal Proteins, Non-Histone / metabolism
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / genetics
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DNA (Cytosine-5-)-Methyltransferases / metabolism
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DNA Methylation / drug effects
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DNA Methyltransferase 3A
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DNA Methyltransferase 3B
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Embryo, Mammalian / metabolism
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Embryonic Development / genetics*
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Embryonic Development / physiology
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Epigenesis, Genetic
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Fibroblasts / metabolism
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Gene Expression Regulation, Developmental / drug effects
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Heterochromatin / metabolism
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism*
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Histones / metabolism
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Homeodomain Proteins / genetics
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Methylation / drug effects
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Mice
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Mice, Knockout
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Models, Genetic
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Nanog Homeobox Protein
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Octamer Transcription Factor-3 / genetics
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Octamer Transcription Factor-3 / metabolism*
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Promoter Regions, Genetic / genetics
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Protein Methyltransferases
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Tretinoin / pharmacology
Substances
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Dnmt3a protein, mouse
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Heterochromatin
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Histones
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Homeodomain Proteins
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Nanog Homeobox Protein
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Nanog protein, mouse
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Octamer Transcription Factor-3
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Chromobox Protein Homolog 5
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Tretinoin
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Histone Methyltransferases
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Protein Methyltransferases
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNA Methyltransferase 3A
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Histone-Lysine N-Methyltransferase