Suppressive Effect of Receptor-interacting Protein 140 on Coregulator Binding to Retinoic Acid Receptor Complexes, Histone-modifying Enzyme Activity, and Gene Activation

Xinli Hu, Yixin Chen, Mariya Farooqui, Mary C. Thomas, Cheng Ming Chiang, Li Na Wei

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 RARβ2 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.

Original languageEnglish (US)
Pages (from-to)319-325
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number1
DOIs
StatePublished - Jan 2 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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