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Cited by 210Genomics and Chromatin DynamicsChromatin Remodeling and CancerHematopoietic Stem Cell Transplantation

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

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Cuartero, Sergi, Weiss, Felix D., Dharmalingam, Gopuraja, Guo, Ya, Ing-Simmons, Elizabeth, Masella, Silvia, Robles-Rebollo, Irene, Xiao, Xiaolin +14 more·2018·Nature Immunology
DOI 10.1038/s41590-018-0184-1PMC PMC6195188
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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.

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  • Cohesin depletion significantly suppresses the activation of inducible genes, especially when the enhancer is located at a significant distance from the promoter.

    “At the same time, cohesin depletion significantly suppresses the activation of inducible genes, especially when the enhancer is located at a significant distance from the promoter [120,121,122].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [122]

    The Discussion (page unavailable) says cohesin is critically required for inducible gene expression in primary myeloid cells, supporting the claim that depletion impairs activation. But the Results section on partial rescue (page unavailable) links cohesin dependence to genes near enhancers; our copy does not establish that suppression is especially strong when an enhancer is far from its promoter. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Cohesin/CTCF-associated enhancers are good candidates for pioneer enhancers, most importantly because of the selective requirement of cohesin for inducible gene control.

    “Theoretically, cohesin/CTCF-associated enhancers are good candidates for pioneer enhancers for a number of reasons, most important of which is the selective requirement of cohesin for inducible gene control [513].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [513]

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References 90 · Cited by 210

Research works printed but not linked: 72

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Authors
Cuartero, S., Weiss, F. D., Dharmalingam, G., Guo, Y., Ing-Simmons, E., Masella, S., Robles-Rebollo, I., Xiao, X., Wang, Y.-F., Barozzi, I., Djeghloul, D., Amano, M. T., Niskanen, H., Petretto, E., Dowell, R. D., Tachibana, K., Kaikkonen, M. U., Nasmyth, K. A., Lenhard, B., Natoli, G., Fisher, A. G., & Merkenschlager, M.
Affiliations
  • MRC London Institute of Medical Sciences (GB)
  • European Institute of Oncology (IT)
  • Imperial College London (GB)
  • Hospital Sírio-Libanês (BR)
  • University of Eastern Finland (FI)
  • Duke-NUS Medical School (SG)
  • University of Colorado Boulder (US)
  • University of Oxford (GB)
  • Humanitas University (IT)
Corresponding author
Merkenschlager, Matthias
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2018-08-20
Volume
19
Issue
9
Pages
932-941
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/s41590-018-0184-1
PMC
PMC6195188
OpenAlex
W2886894187
Cited by
210
References
90
Citations by year
2026: 21 · 2025: 24 · 2024: 17 · 2023: 29 · 2022: 32 · 2021: 33 · 2020: 30 · 2019: 22 · 2018: 2
FWCI
7.60
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion)
  • HAL (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion)
Funders
  • Wellcome Trust (078241/Z/05/Z, 107935/Z/15/Z, 099276/Z/12/Z, 078241, 099276, 692789)
  • Cancer Research UK (12386, 26747)
  • Medical Research Council (MC_EX_MR/S300009/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
cohesin, hematopoietic stem and progenitor cells, myeloid differentiation, macrophages, inducible gene expression, enhancer activity, inflammatory gene expression, CTCF, chromatin looping, 3D genome organization, acute myeloid leukemia, cohesin mutations
MeSH terms
Cell Self Renewal, Cohesins, Animals, Cell Differentiation, Cells, Cultured, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Inflammation, Lipopolysaccharides, Macrophages, Mutation, Nuclear Proteins, Phosphoproteins, Leukemia, Myeloid, Acute, Mice, Knockout, Cell Cycle Proteins, Mice, High-Throughput Nucleotide Sequencing

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