Characterization of Four Autonomous Repression Domains in the Corepressor Receptor Interacting Protein 140

Mark Christian,Jennifer M.A Tullet,Malcolm G Parker

doi:10.1074/jbc.m313906200

Mark Christian, Jennifer M.A Tullet + Show 1 more

Open Access

https://doi.org/10.1074/jbc.m313906200

Copy DOI

Journal: Journal of Biological Chemistry	Publication Date: Apr 1, 2004
Citations: 69	License type: cc-by

Affiliation: Imperial College London

Abstract

Receptor interacting protein (RIP) 140 is a corepressor that can be recruited to nuclear receptors by means of LXXLL motifs. We have characterized four distinct autonomous repression domains in RIP140, termed RD1-4, that are highly conserved in mammals and birds. RD1 at the N terminus represses transcription in the presence of trichostatin A, suggesting that it functions by a histone deacetylase (HDAC)-independent mechanism. The repressive activity of RD2 is dependent upon carboxyl-terminal binding protein recruitment to two specific binding sites. Use of specific inhibitors indicates that RD2, RD3, and RD4 are capable of functioning by HDAC-dependent and HDAC-independent mechanisms, depending upon cell type.

Highlights

The ability of nuclear receptors to regulate transcription from target genes depends on the recruitment of cofactors that initiate chromatin remodelling and the assembly of the transcription machinery
RIP140 Contains Multiple Autonomous Repression Domains—We initially demonstrated that the ability of RIP140 to inhibit estrogen-stimulated transcription from an estrogen responsive element (ERE)-based reporter gene could be achieved by both the N-terminal and C-terminal halves of the protein (Fig. 1A)
RIP140 is a ligand-dependent corepressor of nuclear receptors that may inhibit transcription from target genes by competing with essential coactivators or by active repression following the recruitment of additional proteins

Summary

Introduction

The ability of nuclear receptors to regulate transcription from target genes depends on the recruitment of cofactors that initiate chromatin remodelling and the assembly of the transcription machinery. We have investigated the function of RIP140 as a corepressor by mapping the boundaries of autonomous repression domains and determining the contribution of HDAC and CtBP binding to their ability to repress transcription. The ability of both halves of RIP140 to inhibit transcription from the reporter gene in trans indicates that the protein contains at least two autonomous repression domains.

Results

Conclusion