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Cited by 41Genomics and Chromatin DynamicsChromatin Remodeling and CancerEpigenetics and DNA Methylation

Thrombopoietin signaling to chromatin elicits rapid and pervasive epigenome remodeling within poised chromatin architectures

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Comoglio, Federico, Park, Hyun Jung, Schoenfelder, Stefan, Barozzi, Iros, Bode, Daniel, Fraser, Peter, Green, Anthony R.·2018·Genome Research
DOI 10.1101/gr.227272.117PMC PMC5848609

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Abstract

Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis -regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relationship between cis -regulatory activity and chromatin architecture. We show that TPO profoundly alters the transcriptome of HSPCs, with key hematopoietic regulators being transcriptionally repressed within 30 min of TPO. By examining cis -regulatory dynamics and chromatin architectures, we demonstrate that these changes are accompanied by rapid and extensive epigenome remodeling of cis -regulatory landscapes that is spatially coordinated within topologically associating domains (TADs). Moreover, TPO-responsive enhancers are spatially clustered and engage in preferential homotypic intra- and inter-TAD interactions that are largely refractory to TPO signaling. By further examining the link between cis -regulatory dynamics and chromatin looping, we show that rapid modulation of cis -regulatory activity is largely independent of chromatin looping dynamics. Finally, we show that, although activated and repressed cis -regulatory elements share remarkably similar DNA sequence compositions, transcription factor binding patterns accurately predict rapid cis -regulatory responses to TPO.

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  • Enhancers that control the transcription of many inducible genes are often located in close spatial proximity to these genes in the nuclear space, even in the absence of an inducer.

    “Enhancers that control the transcription of many inducible genes are often located in close spatial proximity to these genes in the nuclear space, even in the absence of an inducer [81,125].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [125]

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Cited by

Sorted by citations

Authors
Comoglio, F., Park, H. J., Schoenfelder, S., Barozzi, I., Bode, D., Fraser, P., & Green, A. R.
Affiliations
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
  • Babraham Institute (GB)
  • Lawrence Berkeley National Laboratory (US)
  • Florida State University (US)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2018-02-02
Volume
28
Issue
3
Pages
295-309
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.227272.117
PMC
PMC5848609
OpenAlex
W2952829451
Cited by
41
References
16
Citations by year
2025: 1 · 2024: 4 · 2023: 9 · 2022: 11 · 2021: 7 · 2020: 3 · 2019: 5 · 2018: 1
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • EMBO long-term (1305-2015)
  • Marie Curie Actions (LTFCOFUND2013/GA-2013-609409)
  • UK Biotechnology and Biological Sciences Research Council (BB/J004480/1)
  • Bloodwise (13003)
  • Wellcome Trust (104710/Z/14/Z)
  • Medical Research Council
  • Kay Kendall Leukaemia Fund
  • Cambridge NIHR Biomedical Research Center
  • Cambridge Experimental Cancer Medicine Centre
  • Leukemia and Lymphoma Society of America (07037)
  • MRC
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
thrombopoietin signaling, cis-regulatory elements, chromatin structure, topologically associating domains, enhancers, chromatin looping, hematopoietic stem and progenitor cells, megakaryopoiesis, transcriptional repression, transcription factor binding, cytokine signaling
MeSH terms
Epigenome, Animals, Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Hematopoietic Stem Cells, Humans, Thrombopoietin, Signal Transduction, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Mice, Transcriptome

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