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PMID:15832170

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Citation

Hartman, HB, Yu, J, Alenghat, T, Ishizuka, T and Lazar, MA (2005) The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3. EMBO Rep. 6:445-51

Abstract

Ligands for nuclear receptors facilitate the exchange of co-repressors for coactivators, leading to chromatin modifications that favour the activation of gene transcription. Here, we show that the repressed state of an endogenous retinoic acid-regulated gene is quickly re-established after ligand removal. As expected, repression is characterized by recruitment of N-CoR/SMRT-HDAC3 (histone deacetylase 3) co-repressor complexes, leading to local histone hypoacetylation. The achievement of the repressed state involves the ordered deacetylation of lysines in H4 tails. This order is determined by the inherent substrate specificity of HDAC3, and unexpectedly predicts the binding preference of N-CoR/SMRT for submaximally acetylated H4 tails. The match between the specificity of acetyl-histone deacetylation by HDAC3 and the histone-binding preference of N-CoR/SMRT allows the co-repressor complex to stabilize and propagate repression of nuclear hormone receptor gene targets.

Links

PubMed PMC1299301 Online version:10.1038/sj.embor.7400391

Keywords

3T3-L1 Cells; Acetylation; Animals; Chromatin/metabolism; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Histone Code; Histone Deacetylases/metabolism; Histones/metabolism; Ligands; Mice; Mucoproteins/metabolism; Nuclear Proteins/metabolism; Nuclear Receptor Co-Repressor 1; Nuclear Receptor Co-Repressor 2; Protein Binding; Receptors, Retinoic Acid/genetics; Receptors, Retinoic Acid/metabolism; Repressor Proteins/metabolism; Substrate Specificity; Tretinoin/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:HDAC3

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:HDAC3

involved_in

GO:0016575: histone deacetylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NCOR2

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:NCOR2

part_of

GO:0000118: histone deacetylase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CBP

enables

GO:0003682: chromatin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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