Abstract
Retinoic acid (RA) induces embryonic stem cell differentiation. The effects of RA are mediated by retinoic acid receptors (RARs) that promote epigenetic changes controlling gene transcription. We show here that RARγ, in the absence of the ligand RA, is required for deposition of the histone variant H2A.Z and the polycomb group protein Suz12 at RA target genes, and that in embryonic stem cells both RARγ and Suz12 exist in a multi-protein complex in the absence of ligand. Addition of RA causes removal of H2A.Z and Suz12 from RARγ target genes when the genes are transcriptionally activated.
© 2010 Wiley-Liss, Inc.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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Cell Differentiation / drug effects
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Cells, Cultured
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Cytochrome P-450 Enzyme System / genetics
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Cytochrome P-450 Enzyme System / metabolism
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Embryonic Stem Cells / cytology
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Embryonic Stem Cells / drug effects
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Embryonic Stem Cells / physiology*
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Epigenesis, Genetic / drug effects
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Gene Expression Regulation / drug effects
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Histones / genetics
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Histones / metabolism*
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Mice
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Mice, Knockout
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Polycomb Repressive Complex 2
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Promoter Regions, Genetic
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Retinoic Acid 4-Hydroxylase
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Retinoic Acid Receptor gamma
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Tretinoin / metabolism
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Tretinoin / pharmacology
Substances
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CCAAT-Enhancer-Binding Proteins
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CEBPA protein, mouse
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Histones
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Receptors, Retinoic Acid
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Repressor Proteins
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Suz12 protein, mouse
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histone H2A.F-Z
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Tretinoin
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Cytochrome P-450 Enzyme System
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Retinoic Acid 4-Hydroxylase
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Polycomb Repressive Complex 2