Mediator-Regulated Transcription through the +1 Nucleosome

• Published in: Molecular cell Vol. 48; no. 6; pp. 837 - 848
• Main Authors: Nock, Adam, Ascano, Janice M., Barrero, Maria J., Malik, Sohail
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.12.2012
• Subjects: Base Sequence; Cell-Free System; Chromosomal Proteins, Non-Histone - chemistry; cofactors; DNA; DNA - chemistry; DNA-Binding Proteins - chemistry; genes; High Mobility Group Proteins - chemistry; Histones - chemistry; in vitro studies; Mediator Complex - chemistry; nucleosomes; Nucleosomes - chemistry; p300-CBP Transcription Factors - chemistry; Promoter Regions, Genetic; RNA Polymerase II - chemistry; transcription (genetics); Transcription Factors - chemistry; Transcription Factors, General - chemistry; Transcription Initiation Site; Transcription, Genetic; Transcriptional Elongation Factors - chemistry
• DOI: 10.1016/j.molcel.2012.10.009
• ISSN: 1097-2765

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. ► Development of an in vitro system to analyze transcription through a +1 nucleosome ► There is functional interplay between Mediator and chromatin cofactors ► SII induces reiterative oligomeric RNA synthesis by promoter-bound Pol II ► Mediator translates this activity of SII into processive transcription