title: PARP1 orchestrates variant histone exchange in signal-mediated transcriptional activation.
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.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Donnell
authors.forename: Shen-Hsi
authors.initials: SH
authors.lastname: Yang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Sharrocks
mesh_terms: D042002:Chromatin Assembly and Disassembly; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D051839:NFI Transcription Factors / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D006657:Histones; D051839:NFI Transcription Factors; D009707:Nucleosomes; D016760:Proto-Oncogene Proteins c-fos; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases