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The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Diamanti, Evangelia 

Abstract

As cells exit the pluripotent state and begin to commit to a specific lineage they must activate genes appropriate for that lineage while silencing genes associated with pluripotency and preventing activation of lineage-inappropriate genes. The Nucleosome Remodelling and Deacetylation (NuRD) complex is essential for pluripotent cells to successfully undergo lineage commitment. NuRD controls nucleosome density at regulatory sequences to facilitate transcriptional responses, and also has been shown to prevent unscheduled transcription (transcriptional noise) in undifferentiated pluripotent cells. How these activities combine to ensure cells engage a gene expression program suitable for successful lineage commitment has not been determined. Here we show that NuRD is not required to silence all genes. Rather it restricts expression of genes primed for activation upon exit from the pluripotent state, but maintains them in a transcriptionally permissive state in self-renewing conditions which facilitates their subsequent activation upon exit from naïve pluripotency. We further show that NuRD coordinates gene expression changes, which acts to maintain a barrier between different stable states. Thus NuRD-mediated chromatin remodelling serves multiple functions, including reducing transcriptional noise, priming genes for activation and coordinating the transcriptional response to facilitate lineage commitment.

Description

Keywords

Chromatin, Embryonic Stem Cell, Lineage Commitment, MBD3, NuRD, Transcription

Journal Title

Biol Open

Conference Name

Journal ISSN

2046-6390
2046-6390

Volume Title

Publisher

The Company of Biologists
Sponsorship
Isaac Newton Trust (Minute 17.24 (aa))
Isaac Newton Trust (22.39(g))
Isaac Newton Trust (1540(L))
Medical Research Council (MR/R009759/1)
Wellcome Trust (098021/Z/11/Z)
Wellcome Trust (206291/Z/17/Z)
Isaac Newton Trust Microsoft Research