PARP1 orchestrates variant histone exchange in signal-mediated transcriptional activation

Amanda O'Donnell, Shen Hsi Yang, Andrew D. Sharrocks

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Transcriptional activation is accompanied by multiple molecular events that remodel the local chromatin environment in promoter regions. These molecular events are often orchestrated in response to the activation of signalling pathways, as exemplified by the response of immediate early genes such as FOS to ERK MAP kinase signalling. Here, we demonstrate that inducible NFI recruitment permits PARP1 binding to the FOS promoter by a mutually reinforcing loop. PARP1 and its poly(ADP-ribosyl)ation activity are required for maintaining FOS activation kinetics. We also show that the histone variant H2A.Z associates with the FOS promoter and acts in a transcription-suppressive manner. However, in response to ERK pathway signalling, H2A.Z is replaced by H2A; PARP1 activity is required to promote this exchange. Thus, our work has revealed an additional facet of PARP1 function in promoting dynamic remodelling of promoter-associated nucleosomes to allow transcriptional activation in response to cellular signalling. © 2013 EUROPEAN MOLECULAR BIOLOGY ORGANIZATION.
    Original languageEnglish
    Pages (from-to)1084-1091
    Number of pages7
    JournalEMBO reports
    Volume14
    Issue number12
    DOIs
    Publication statusPublished - Dec 2013

    Keywords

    • Chromatin
    • H2A.Z
    • Immediate early genes
    • MAP kinase signalling
    • PARP

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