Divergent wiring of repressive and active chromatin interactions between mouse embryonic and trophoblast lineages
Open accessAbstract
The establishment of the embryonic and trophoblast lineages is a developmental decision underpinned by dramatic differences in the epigenetic landscape of the two compartments. However, it remains unknown how epigenetic information and transcription factor networks map to the 3D arrangement of the genome, which in turn may mediate transcriptional divergence between the two cell lineages. Here, we perform promoter capture Hi-C experiments in mouse trophoblast (TSC) and embryonic (ESC) stem cells to understand how chromatin conformation relates to cell-specific transcriptional programmes. We find that key TSC genes that are kept repressed in ESCs exhibit interactions between H3K27me3-marked regions in ESCs that depend on Polycomb repressive complex 1. Interactions that are prominent in TSCs are enriched for enhancer–gene contacts involving key TSC transcription factors, as well as TET1, which helps to maintain the expression of TSC-relevant genes. Our work shows that the first developmental cell fate decision results in distinct chromatin conformation patterns establishing lineage-specific contexts involving both repressive and active interactions.
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3C-derived methods have detected multitudes of enhancer-promoter loops in many human and mouse cell types.
“These enrichment methods have detected multitudes of enhancer–promoter loops in many human and mouse cell types [243, 286–291].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [287]
The Results sections report promoter capture Hi-C detection of hundreds of thousands of promoter contacts in mouse embryonic stem and trophoblast stem cells, including contacts with enhancers. The Introduction mentions studies in human cells, but this paper does not establish the claim's broader scope of multitudes of enhancer–promoter loops across many human and mouse cell types. The supplied copy gives no page numbers. (LLM, conf=0.82)
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- Authors
- Schoenfelder, S., Mifsud, B., Senner, C. E., Todd, C. D., Chrysanthou, S., Darbo, E., Hemberger, M., & Branco, M. R.
- Affiliations
- Babraham Institute (GB)
- Queen Mary University of London (GB)
- Corresponding author
- Hemberger, Myriam
- Branco, Miguel R.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-10-10
- Volume
- 9
- Issue
- 1
- Pages
- 4189-4189
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6180096
- OpenAlex
- W2894824533
- Cited by
- 54
- References
- 57
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 10 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 7 · 2018: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (101225/Z/13/Z)
- Babraham Institute The Medical College of Saint Bartholomew’s Hospital Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- embryonic stem cells, 3D genome organization, PRC1, H3K27me3, TET1, enhancer-gene interactions, promoter capture Hi-C, epigenetic landscape, transcriptional repression, mouse embryo
- MeSH terms
- Mouse Embryonic Stem Cells, Animals, Chromatin, DNA-Binding Proteins, Embryo, Mammalian, Enhancer Elements, Genetic, Histones, Lysine, Methylation, Mice, Inbred ICR, Proto-Oncogene Proteins, Trophoblasts, Genome, Gene Expression Regulation, Developmental, Cell Lineage, Mice, Polycomb Repressive Complex 1
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