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

Summary

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.

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Highlights

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  NuRD increases nucleosome density, expelling TFs or inhibiting recruitment

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  NuRD displaces RNA Pol II from TSSs, reducing nascent transcription

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  Local gains in TF and Mediator occupancy can be indirect effects of NuRD activity

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  Resetting protein binding at regulatory elements can promote or suppress transcription

Abstract

Bornelöv et al. define how NuRD, an abundant chromatin remodeling complex, fine-tunes gene expression. NuRD controls nucleosome positioning across regulatory elements genome-wide, controlling access of DNA-binding proteins to enhancers and promoters. This resetting of the transcription factor repertoire at regulatory elements restricts expression from some loci and induces transcription at others.