title: Mediator-regulated transcription through the +1 nucleosome.
abstract: Many genes are regulated at the level of a Pol II that is recruited to a nucleosome-free region upstream of the +1 nucleosome. How the Mediator coactivator complex, which functions at multiple steps, affects transcription through the promoter proximal region, including this nucleosome, remains largely unaddressed. We have established a fully defined in vitro assay system to delineate mechanisms for Pol II transit across the +1 nucleosome. Our results reveal cooperative functions of multiple cofactors, particularly of Mediator and elongation factor SII, in transcribing into this nucleosome. This is achieved, in part, through an unusual activity of SII that alters the intrinsic catalytic properties of promoter-proximal Pol II and, in concert with the Mediator, leads to enhancement in transcription of nucleosomal DNA. Our data provide additional mechanistic bases for Mediator function after recruitment of Pol II and, potentially, for regulation of genes controlled via nucleosome-mediated promoter-proximal pausing.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Nock
authors.forename: Janice M
authors.initials: JM
authors.lastname: Ascano
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barrero
authors.forename: Sohail
authors.initials: S
authors.lastname: Malik
mesh_terms: D001483:Base Sequence; D002474:Cell-Free System; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry; D006609:High Mobility Group Proteins / Q000737:chemistry; D006657:Histones / Q000737:chemistry; D056892:Mediator Complex / Q000737:chemistry*; D009707:Nucleosomes / Q000737:chemistry*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry; D035165:Transcription Factors, General / Q000737:chemistry; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000737:chemistry; D050880:p300-CBP Transcription Factors / Q000737:chemistry
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D006657:Histones; D056892:Mediator Complex; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D035165:Transcription Factors, General; D035602:Transcriptional Elongation Factors; C018648:transcription factor S-II; D004247:DNA; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II