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Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation

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Title: Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation
Authors: Merkenschlager, M
Cuartero, S
Weiss, F
Dharmalingam, G
Guo, Y
Ing-Simmons, E
Masella, S
Robles-Rebollo, I
Xiao, X
Barozzi, I
Djeghloul, D
Amano, M
Niskanen, H
Petretto, E
Dowell, R
Tachibana, K
Kaikkonen, M
Nasmyth, K
Lenhard, B
Natoli, G
Fisher, A
Item Type: Journal Article
Abstract: Cohesin is important for 3D genome organization. Nevertheless, even the complete removal of cohesin has surprisingly little impact on steady-state gene transcription and enhancer activity. Here we show that cohesin is required for the core transcriptional response of primary macrophages to microbial signals, and for inducible enhancer activity that underpins inflammatory gene expression. Consistent with a role for inflammatory signals in promoting myeloid differentiation of hematopoietic stem and progenitor cells (HPSCs), cohesin mutations in HSPCs led to reduced inflammatory gene expression and increased resistance to differentiation-inducing inflammatory stimuli. These findings uncover an unexpected dependence of inducible gene expression on cohesin, link cohesin with myeloid differentiation, and may help explain the prevalence of cohesin mutations in human acute myeloid leukemia.
Issue Date: 20-Aug-2018
Date of Acceptance: 17-Jul-2018
URI: http://hdl.handle.net/10044/1/62818
DOI: https://dx.doi.org/10.1038/s41590-018-0184-1
ISSN: 1529-2908
Publisher: Nature Publishing Group
Start Page: 932
End Page: 941
Journal / Book Title: Nature Immunology
Volume: 19
Copyright Statement: © 2018 Springer Nature. All rights reserved.
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Funder's Grant Number: 099276/Z/12/Z
PO4050659629
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
CELL IDENTITY GENES
STEM-CELLS
INSULATED NEIGHBORHOODS
TRANSCRIPTION FACTORS
REVEALS PRINCIPLES
CHROMATIN DOMAINS
CHRONIC INFECTION
DNA-BINDING
GENOME
COMPLEX
1107 Immunology
Publication Status: Published
Online Publication Date: 2018-08-20
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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