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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: 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
STEM-CELLS
INSULATED NEIGHBORHOODS
TRANSCRIPTION FACTORS
REVEALS PRINCIPLES
CHROMATIN DOMAINS
GENOME
COMPLEX
ACTIVATION
CTCF
ORGANIZATION
Animals
Cell Cycle Proteins
Cell Differentiation
Cell Self Renewal
Cells, Cultured
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Gene Expression Regulation
Hematopoietic Stem Cells
High-Throughput Nucleotide Sequencing
Humans
Inflammation
Leukemia, Myeloid, Acute
Lipopolysaccharides
Macrophages
Mice
Mice, Knockout
Mutation
Nuclear Proteins
Phosphoproteins
Hematopoietic Stem Cells
Cells, Cultured
Macrophages
Animals
Mice, Knockout
Humans
Mice
Inflammation
Lipopolysaccharides
Cell Cycle Proteins
DNA-Binding Proteins
Nuclear Proteins
Chromosomal Proteins, Non-Histone
Phosphoproteins
Cell Differentiation
Gene Expression Regulation
Mutation
Leukemia, Myeloid, Acute
High-Throughput Nucleotide Sequencing
Cell Self Renewal
1107 Immunology
Immunology
Publication Status: Published
Online Publication Date: 2018-08-20
Appears in Collections:Department of Surgery and Cancer
Institute of Clinical Sciences
Faculty of Medicine