PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. - Archive ouverte HAL Access content directly
Journal Articles Molecular Cell Year : 2005

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

Abstract

We show that PARP-1 is indispensable to retinoic acid receptor (RAR)-mediated transcription from the RARbeta2 promoter in a highly purified, reconstituted transcription system and that RA-inducible expression of all RARbeta 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.

Dates and versions

hal-00187716 , version 1 (15-11-2007)

Identifiers

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Rushad Pavri, Brian Lewis, Tae-Kyung Kim, F Jeffrey Dilworth, Hediye Erdjument-Bromage, et al.. PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator.. Molecular Cell, 2005, 18 (1), pp.83-96. ⟨10.1016/j.molcel.2005.02.034⟩. ⟨hal-00187716⟩
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