A high-resolution map of transcriptional repression

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Title: A high-resolution map of transcriptional repression
Author(s): Liang, Z
Brown, KE
Carroll, T
Taylor, B
Vidal, IF
Hendrich, B
Rueda, D
Fisher, AG
Merkenschlager, M
Item Type: Journal Article
Abstract: Turning genes on and off is essential for development and homeostasis, yet little is known about the sequence and causal role of chromatin state changes during the repression of active genes. This is surprising, as defective gene silencing underlies developmental abnormalities and disease. Here we delineate the sequence and functional contribution of transcriptional repression mechanisms at high temporal resolution. Inducible entry of the NuRD-interacting transcriptional regulator Ikaros into mouse pre-B cell nuclei triggered immediate binding to target gene promoters. Rapid RNAP2 eviction, transcriptional shutdown, nucleosome invasion, and reduced transcriptional activator binding required chromatin remodeling by NuRD-associated Mi2beta/CHD4, but were independent of HDAC activity. Histone deacetylation occurred after transcriptional repression. Nevertheless, HDAC activity contributed to stable gene silencing. Hence, high resolution mapping of transcriptional repression reveals complex and interdependent mechanisms that underpin rapid transitions between transcriptional states, and elucidates the temporal order, functional role and mechanistic separation of NuRD-associated enzymatic activities.
Publication Date: 20-Mar-2017
Date of Acceptance: 15-Mar-2017
URI: http://hdl.handle.net/10044/1/46061
DOI: https://dx.doi.org/10.7554/eLife.22767
ISSN: 2050-084X
Publisher: ELIFE SCIENCES PUBLICATIONS LTD
Journal / Book Title: ELIFE
Volume: 6
Copyright Statement: © 2017 Liang et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Sponsor/Funder: The Leverhulme Trust
The Leverhulme Trust
Medical Research Council (MRC)
Funder's Grant Number: RPG-2016-214
RPG-2016-214
Chain Florey 2016-21
Keywords: Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
CHROMATIN REMODELING COMPLEXES
ACUTE LYMPHOBLASTIC-LEUKEMIA
B-CELL DIFFERENTIATION
DNA-BINDING PROTEINS
GENE-REGULATION
CENTROMERIC HETEROCHROMATIN
GENOME-WIDE
STEM-CELLS
IKAROS
ACTIVATION
B cell
Ikaros
chromosomes
corepressor complex
gene silencing
genes
mouse
transcriptional repression
Publication Status: Published
Article Number: ARTN e22767
Open Access location: https://elifesciences.org/content/6/e22767
Appears in Collections:Clinical Sciences
Molecular Sciences
Department of Medicine



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