Abstract
rRNA genes (rDNA) exist in two distinct epigenetic states, active promoters being unmethylated and marked by euchromatic histone modifications, whereas silent ones are methylated and exhibit heterochromatic features. Here we show that the nucleosome remodeling and deacetylation (NuRD) complex establishes a specific chromatin structure at rRNA genes that are poised for transcription activation. The promoter of poised rRNA genes is unmethylated, associated with components of the preinitiation complex, marked by bivalent histone modifications and covered by a nucleosome in the "off" position, which is refractory to transcription initiation. Repression of rDNA transcription in growth-arrested and differentiated cells correlates with elevated association of NuRD and increased levels of poised rRNA genes. Reactivation of transcription requires resetting the promoter-bound nucleosome into the "on" position by the DNA-dependent ATPase CSB (Cockayne syndrome protein B). The results uncover a unique mechanism by which ATP-dependent chromatin remodeling complexes with opposing activities establish a specific chromatin state and regulate transcription.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism
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Animals
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Cell Differentiation / physiology
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Chromatin / genetics
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Chromatin / metabolism*
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DNA Helicases / genetics
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DNA Helicases / metabolism
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DNA Repair Enzymes / genetics
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DNA Repair Enzymes / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Epigenesis, Genetic / physiology
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Genes, rRNA / genetics*
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Histones / genetics
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Histones / metabolism*
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Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics
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Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism*
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Mice
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NIH 3T3 Cells
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Nucleosomes / genetics
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Nucleosomes / metabolism*
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Poly-ADP-Ribose Binding Proteins
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RNA Polymerase I / genetics
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RNA Polymerase I / metabolism
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RNA, Ribosomal / genetics
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Transcription Factors
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Transcriptional Activation / physiology*
Substances
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Chromatin
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DNA-Binding Proteins
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Histones
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Nucleosomes
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Poly-ADP-Ribose Binding Proteins
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RNA, Ribosomal
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Transcription Factors
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Ttf1 protein, mouse
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RNA Polymerase I
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Adenosine Triphosphatases
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Mi-2beta protein, mouse
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DNA Helicases
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Ercc6 protein, mouse
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DNA Repair Enzymes