3D Chromosome Regulatory Landscape of Human Pluripotent Cells
Open accessAbstract
In this study, we describe the 3D chromosome regulatory landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associating domains (TADs) that are largely preserved during the transition between the naive and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.
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TADs correspond to only one level of a hierarchy of loop domains, with super-/sub-TADs and insulated neighbourhoods potentially corresponding to other levels.
“TADs correspond to only one level of a hierarchy of such “loop domains”, with super-/sub-TADs and insulated neighbourhoods potentially corresponding to other levels [434, 441, 442].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [434]
The Discussion describes TADs as nested sets of CTCF–CTCF loops, and Results (“Schematics of TAD structures”) identifies insulated neighborhoods within TADs. These passages support multiple levels of loop organization, but do not establish the proposed place of super-TADs in that hierarchy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredMetazoan genomes are organised into megabase-scale segregated domains that are often invariant between cell types, termed TADs.
“metazoan genomes are organised into megabase-scale segregated domains that are often invariant between cell types, termed topologically associating domains (TADs) [432–434].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [434]
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Cites
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- Authors
- Ji, X., Dadon, D. B., Powell, B. E., Fan, Z. P., Borges-Rivera, D., Shachar, S., Weintraub, A. S., Hnisz, D., Pegoraro, G., Lee, T. I., Misteli, T., Jaenisch, R., & Young, R. A.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- National Institutes of Health (US)
- Corresponding author
- Jaenisch, Rudolf
- Young, Richard A.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 18
- Issue
- 2
- Pages
- 262-275
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4848748
- OpenAlex
- W2192926654
- Cited by
- 400
- References
- 19
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 25 · 2023: 23 · 2022: 31 · 2021: 46 · 2020: 43 · 2019: 49 · 2018: 49 · 2017: 58 · 2016: 41 · 2015: 1
- FWCI
- 21.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH104610)
- National Human Genome Research Institute (HG002668, R25HG007631, R01HG002668)
- National Institute of General Medical Sciences (T32GM007287)
- National Institute of Neurological Disorders and Stroke (R01NS088538)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD045022, HD045022, R37HD045022)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- human embryonic stem cells, naive pluripotency, primed pluripotency, enhancers, insulators, cohesin, topologically associating domains, enhancer-promoter interactions, cell state transitions, chromatin structure
- MeSH terms
- Human Embryonic Stem Cells, CCCTC-Binding Factor, Cohesins, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Chromosomes, Human, Disease, DNA, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Nucleic Acid Conformation, Repressor Proteins, Transcription Factors, Cell Cycle Proteins, MicroRNAs, Insulator Elements, Pluripotent Stem Cells
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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