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

doi:10.1016/j.molcel.2005.02.034

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 journal › Article › peer-review

193 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 language	English (US)
Pages (from-to)	83-96
Number of pages	14
Journal	Molecular cell
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.molcel.2005.02.034
State	Published - Apr 1 2005

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2005.02.034

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@article{bde94ba7aa484bd6a72d9955cb015601,

title = "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 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.",

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

note = "Funding Information: We thank Dr. Dylan Taatjes for generously providing purified CRSP complex. We thank Dr. Joe Fondell for f-TRα baculovirus and the HeLa α2 cell line expressing f-TRα. We thank Drs. Josiane Menissier de Murcia, Lynne Vales, Alejandro Vaquero, and Bing Zhu for helpful comments and suggestions. This work was supported by a grant from the National Institutes of Health (GM37120) and the Howard Hughes Medical Institute to D.R. Work performed at IGBMC was supported by a grant from the Centre National de la Recherche Scientifique (CNRS), INSERM, College de France, and Association pour la Recherche sur le Cancer. G.d.M.{\textquoteright}s laboratory is supported by CNRS, Association pour la Recherche sur le Cancer, La Ligue contre le Cancer, and Commissariat {\`a} l{\textquoteright}Energie Atomique. ",

year = "2005",

month = apr,

day = "1",

doi = "10.1016/j.molcel.2005.02.034",

language = "English (US)",

volume = "18",

pages = "83--96",

journal = "Molecular cell",

issn = "1097-2765",

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T1 - PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator

AU - Pavri, Rushad

AU - Lewis, Brian

AU - Kim, Tae Kyung

AU - Dilworth, F. Jeffrey

AU - Erdjument-Bromage, Hediye

AU - Tempst, Paul

AU - De Murcia, Gilbert

AU - Evans, Ronald

AU - Chambon, Pierre

AU - Reinberg, Danny

N1 - Funding Information: We thank Dr. Dylan Taatjes for generously providing purified CRSP complex. We thank Dr. Joe Fondell for f-TRα baculovirus and the HeLa α2 cell line expressing f-TRα. We thank Drs. Josiane Menissier de Murcia, Lynne Vales, Alejandro Vaquero, and Bing Zhu for helpful comments and suggestions. This work was supported by a grant from the National Institutes of Health (GM37120) and the Howard Hughes Medical Institute to D.R. Work performed at IGBMC was supported by a grant from the Centre National de la Recherche Scientifique (CNRS), INSERM, College de France, and Association pour la Recherche sur le Cancer. G.d.M.’s laboratory is supported by CNRS, Association pour la Recherche sur le Cancer, La Ligue contre le Cancer, and Commissariat à l’Energie Atomique.

PY - 2005/4/1

Y1 - 2005/4/1

N2 - 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.

AB - 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.

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AN - SCOPUS:20144389926

SN - 1097-2765

VL - 18

SP - 83

EP - 96

JO - Molecular cell

JF - Molecular cell

IS - 1

ER -

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

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