TY - JOUR T1 - The Nucleosome Remodelling and Deacetylation complex restricts Mediator access to enhancers to control transcription JF - bioRxiv DO - 10.1101/103192 SP - 103192 AU - Maria Xenophontos AU - Nicola Reynolds AU - Sarah Gharbi AU - Ewan Johnstone AU - Jason Signolet AU - Robin Floyd AU - Meryem Ralser AU - Susanne Bornelöv AU - Sabine Dietmann AU - Remco Loos AU - Paul Bertone AU - Brian Hendrich Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/25/103192.abstract N2 - A number of different chromatin remodelling complexes in mammalian cells are implicated in the control of gene expression. The genetic requirements for many such complex components have been described, and the biochemical activities of complex components characterised in vitro, yet the molecular mechanisms by which these biochemical activities impact transcriptional regulation in vivo remain ill-defined. Using an inducible system with fine temporal resolution, we show that the Nucleosome Remodelling and Deacetylation (NuRD) complex directly regulates chromatin architecture at enhancer regions in ES cells, in turn influencing the activity of RNA polymerase II via Mediator. Through this mechanism NuRD restricts Mediator access to enhancer chromatin during lineage commitment, thereby enabling appropriate transcriptional regulation. In contrast, acetylation levels of histone H3 lysine 27 are not immediately impacted by NuRD activity, correlating with transcriptional response only after expression levels have changed. These findings provide a detailed, molecular picture of genome-wide modulation of lineage-specific transcription by an abundant chromatin remodelling complex. ER -