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The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
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The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
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Paper
The Nucleosome Remodelling and Deacetylation complex coordinates the transcriptional response to lineage commitment in pluripotent cells
2023
Overview
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 while NuRD is not required to silence all genes, its activity is important to restrict expression of genes primed for activation upon exit from the pluripotent state, and that NuRD activity facilitates their subsequent transcriptional activation. 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.Competing Interest StatementSara-Jane Dunn was an employee at Microsoft Research during this study and is currently employed at DeepMind. Neither Microsoft Research nor DeepMind have directed any aspect of the study nor exerted any commercial rights over the results. The authors declare no conflicts of interest.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
