The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3.

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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Hartman HB,Yu J,Alenghat T,Ishizuka T,Lazar MA

doi

10.1038/sj.embor.7400391

keywords:

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

445-51

issue

5

eissn

1469-221X

issn

1469-3178

pii

7400391

journal_volume

6

pub_type

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