The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression.
MetadataShow full item record
Borneloev, S., Reynolds, N., Xenophontos, M., Gharbi, S., Johnstone, E., Floyd, R., Ralser, M., et al. (2018). The Nucleosome Remodeling and Deacetylation Complex Modulates Chromatin Structure at Sites of Active Transcription to Fine-Tune Gene Expression.. Molecular cell, 71 (1), 56-72.e4. https://doi.org/10.1016/j.molcel.2018.06.003
Chromatin remodelling 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 Remodelling 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 remodelling 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 remodelling complex as well as insight into the orchestration of molecular events involved in transcriptional transitions in vivo.
Cell Line, Nucleosomes, Animals, Mice, RNA Polymerase II, Histones, Transcription, Genetic, Gene Expression Regulation, Acetylation, Transcription Initiation Site, Mi-2 Nucleosome Remodeling and Deacetylase Complex, Mouse Embryonic Stem Cells
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.
Wellcome Trust (097922/Z/11/Z)
Wellcome Trust (098021/Z/11/Z)
Wellcome Trust (079249/Z/06/I)
EC FP7 CP (277899)
External DOI: https://doi.org/10.1016/j.molcel.2018.06.003
This record's URL: https://www.repository.cam.ac.uk/handle/1810/283360
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/