PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator

Rushad Pavri, Brian Lewis, Tae Kyung Kim, F. Jeffrey Dilworth, Hediye Erdjument-Bromage, Paul Tempst, Gilbert De Murcia, Ronald Evans, Pierre Chambon, Danny Reinberg

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

We show that PARP-1 is indispensable to retinoic acid receptor (RAR)-mediated transcription from the RARβ2 promoter in a highly purified, reconstituted transcription system and that RA-inducible expression of all RARβ isoforms is abrogated in PARP-1-/- cells in vivo. Importantly, PARP-1 activity was independent of its catalytic domain. PARP-1 directly interacts with RAR and Mediator. Chromatin immunoprecipitation experiments confirmed the presence of PARP-1 and Mediator on RAR-responsive promoters in vivo. Importantly, Mediator was inactive (Cdk8+) under basal conditions but was activated (Cdk8-) upon induction. However, in PARP-1-/- cells, Mediator was retained in its inactive state (Cdk8+) upon induction consistent with the absence of gene expression. PARP-1 became dispensable for ligand-dependent transcription in a chromatin reconstituted transcription assay when Mediator was devoid of the Cdk8 module (CRSP). PARP-1 appears to function as a specificity factor regulating the RA-induced switch of Mediator from the inactive (Cdk8+) to the active (Cdk8-) state in RAR-dependent transcription.

Original languageEnglish (US)
Pages (from-to)83-96
Number of pages14
JournalMolecular cell
Volume18
Issue number1
DOIs
StatePublished - Apr 1 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Pavri, R., Lewis, B., Kim, T. K., Dilworth, F. J., Erdjument-Bromage, H., Tempst, P., De Murcia, G., Evans, R., Chambon, P., & Reinberg, D. (2005). PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Molecular cell, 18(1), 83-96. https://doi.org/10.1016/j.molcel.2005.02.034