Polycomb repressive Complex 1 generates discrete compacted domains that change during differentiation
Open accessAbstract
Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1). These domains changed during differentiation as PRC1 binding changed. Their formation depended upon the Polyhomeotic component of canonical PRC1 and occurred independently of PRC1-catalyzed ubiquitylation. PRC1 domains differ from topologically associating domains in size and boundary characteristics. These domains have the potential to play a key role in transmitting epigenetic silencing of PcG targets by linking PRC1 to formation of a repressive higher-order structure.
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Spatial organization of chromatin, including long-range DNA interactions, plays a key role in controlling gene expression and maintaining cellular identity.
“The spatial organization of chromatin, including a variety of long-range DNA interactions, plays a key role in controlling gene expression and maintaining cellular identity (Gorkin et al., 2014; Kundu et al., 2017; Narendra et al., 2015; Schoenfelder et al., 2015; Zirkel et al., 2018).”
From Loss of epigenetic information as a cause of mammalian aging (2023) · cites this paper as Kundu et al., 2017
The Results (page unavailable) link changes in PRC1-associated chromatin domains to Hox gene derepression during differentiation. The Discussion (page unavailable) hypothesizes that these domains might help silence genes and maintain their silenced state; it does not establish that spatial organization plays a key role in maintaining cellular identity. (LLM, conf=0.84)
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Self-citation
- Authors
- Kundu, S., Ji, F., Sunwoo, H., Jain, G., Lee, J. T., Sadreyev, R. I., Dekker, J., & Kingston, R. E.
- Affiliations
- Harvard University (US)
- University of Massachusetts Chan Medical School (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kingston, Robert E.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 65
- Issue
- 3
- Pages
- 432-446.e5
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5421375
- OpenAlex
- W2585920126
- Cited by
- 333
- References
- 73
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 27 · 2023: 23 · 2022: 45 · 2021: 55 · 2020: 41 · 2019: 48 · 2018: 35 · 2017: 17
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-07-05)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Institutes of Health (5R01GM043901-24, DK107980, HG003143, P30 DK40561, R01-GM090278)
- Howard Hughes Medical Institute
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- 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
- Keywords
- PRC1, Polycomb group proteins, chromatin condensation, polyhomeotic, epigenetic silencing, chromatin looping, topologically associating domains, neural progenitor cells, embryonic stem cells, cell differentiation, chromatin organization, higher-order chromatin structure
- MeSH terms
- Protein Domains, Animals, Cell Differentiation, Cells, Cultured, Chromatin, DNA, Histones, Humans, Homeodomain Proteins, Gene Expression Regulation, Developmental, Epigenesis, Genetic, Mice, Embryonic Stem Cells, Ubiquitination, Neural Stem Cells, Polycomb Repressive Complex 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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