Suppressive effect of receptor-interacting protein 140 on coregulator binding to retinoic acid receptor complexes, histone-modifying enzyme activity, and gene activation.

Gene induction by retinoic acid (RA) is suppressed by overexpression of receptor-interacting protein 140 (RIP140). RIP140-mediated suppression was reversed most effectively by overexpressing the coactivator p300/CREB-binding protein-associated factor (P/CAF). Immunoprecipitation demonstrated coexistence of holoreceptors complexed with RIP140 or P/CAF. Chromatin immunoprecipitation revealed rapid RA-enhanced recruitment of RIP140, but delayed P/CAF ...
recruitment, to an RA-targeted promoter in COS-1 cells supplemented with RIP140. In RA-induced P19 cells, endogenous RIP140 was rapidly (within 4 h) and significantly recruited to both the RARbeta2 and TR2 genes, whereas the peak of endogenous P/CAF recruitment occurred much later (48 h) and to a lesser degree. Consistent with these observations, significant histone acetylation of endogenous RA receptor (RAR) targets was only observed 48 h following RA treatment. In vitro experiments confirmed RA-induced transcription from a chromatin template, which was reduced by adding RIP140. This study presents evidence for coexistence of multiple RAR-coregulator complexes and a preferential RA-induced recruitment of RIP140 to endogenous RAR-targeted promoters after short term RA treatment, which correlates with suppressed induction of RA-regulated gene expression in the presence of RIP140.
Mesh Terms:
Acetyltransferases, Adaptor Proteins, Signal Transducing, Animals, COS Cells, Cell Cycle Proteins, Cercopithecus aethiops, Gene Expression Regulation, Histone Acetyltransferases, Kinetics, Nuclear Proteins, Receptors, Retinoic Acid, Recombinant Proteins, Transcription Factors, Transcriptional Activation, Transfection, Tretinoin, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Jan. 02, 2004
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