The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression.

Change log
Bornelöv, Susanne 
Reynolds, Nicola 
Xenophontos, Maria 
Gharbi, Sarah 
Johnstone, Ewan 

Chromatin remodeling complexes play essential roles in metazoan development through widespread control of gene expression, but the precise molecular mechanisms by which they do this in vivo remain ill defined. Using an inducible system with fine temporal resolution, we show that the nucleosome remodeling and deacetylation (NuRD) complex controls chromatin architecture and the protein binding repertoire at regulatory regions during cell state transitions. This is primarily exerted through its nucleosome remodeling activity while deacetylation at H3K27 follows changes in gene expression. Additionally, NuRD activity influences association of RNA polymerase II at transcription start sites and subsequent nascent transcript production, thereby guiding the establishment of lineage-appropriate transcriptional programs. These findings provide a detailed molecular picture of genome-wide modulation of lineage-specific transcription by an essential chromatin remodeling complex as well as insight into the orchestration of molecular events involved in transcriptional transitions in vivo. VIDEO ABSTRACT.

Mediator, NuRD, RNA polymerase II, chromatin, embryonic stem cells, enhancer, transcription, transcription factor, Acetylation, Animals, Cell Line, Gene Expression Regulation, Histones, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mice, Mouse Embryonic Stem Cells, Nucleosomes, RNA Polymerase II, Transcription Initiation Site, Transcription, Genetic
Journal Title
Mol Cell
Conference Name
Journal ISSN
Volume Title
Elsevier BV
Wellcome Trust (097922/Z/11/Z)
Wellcome Trust (098021/Z/11/Z)
Biotechnology and Biological Sciences Research Council (BB/M004023/1)
Medical Research Council (MC_PC_12009)
Wellcome Trust (079249/Z/06/I)
European Commission (277899)
MX was funded through an EMBL PhD studentship, EJ through a BBSRC PhD studentship and JS through an MRC PhD studentship. Funding in the BH lab was provided by a Wellcome Trust Senior Fellowship and the EU FP7 Integrated Project “4DCellFate.” Funding in the PB lab was provided by EMBL and BBSRC. BH and PB labs further benefit from core funding to the Cambridge Stem Cell Institute from the Wellcome Trust and Medical Research Council.