Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing.
Receptor-interacting protein 140 (RIP140) encodes a histone deacetylase (HDAC) inhibitor-sensitive repressive activity. Direct interaction of RIP140 with HDAC1 and HDAC3 occurs in vitro and in vivo as demonstrated in co-immunoprecipitation and glutathione S-transferase pull-down experiments. The HDAC-interacting domain of RIP140 is mapped to its N-terminal domain, between amino acids 78 and 303 based upon glutathione S-transferase pull-down experiments. In chromatin immunoprecipitation assays, it is demonstrated that histone deacetylation occurs at the chromatin region of the Gal4 binding sites as a result of Gal4 DNA binding domain-tethered RIP expression. The immunocomplexes of RIP140 from cells transfected with RIP140 and HDAC are able to deacetylate histone proteins in vitro. This study presents the first evidence for RIP140 as a negative coregulator for nuclear receptor actions by directly recruiting histone deacetylases and categorizes RIP140 as a novel negative coregulator that is able to directly interact with HDACs.
Wei
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Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. weixx009@maroon.tc.umn.edu
Hu
X
X
Chandra
D
D
Seto
E
E
Farooqui
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D009687:Nuclear Proteins / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D006657:Histones; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C012589:trichostatin A; D014212:Tretinoin; D006655:Histone Deacetylases