A compendium of chromatin contact maps reveals spatially active regions in the human genome
Open accessAbstract
The three-dimensional configuration of DNA is integral to all nuclear processes in eukaryotes, yet our knowledge of the chromosome architecture is still limited. Genome-wide chromosome conformation capture studies have uncovered features of chromatin organization in cultured cells, but genome architecture in human tissues has yet to be explored. Here, we report the most comprehensive survey to date of chromatin organization in human tissues. Through integrative analysis of chromatin contact maps in 21 primary human tissues and cell types, we find topologically associating domains highly conserved in different tissues. We also discover genomic regions that exhibit unusually high levels of local chromatin interactions. These frequently interacting regions (FIREs) are enriched for super-enhancers and are near tissue-specifically expressed genes. They display strong tissue-specificity in local chromatin interactions. Additionally, FIRE formation is partially dependent on CTCF and the Cohesin complex. We further show that FIREs can help annotate the function of non-coding sequence variants.
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A false discovery rate of 1 × 10-5 was used to define significant chromatin interactions, based on previous recommendations modified for the cell lines used.
“We used an FDR of 1 × 10 -5 to define significant interactions, based on previous recommendations 51 modified to account for the differences in cell lines used here.”
From Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence (2018) · cites this paper as [51]
The Experimental Procedures ('Identification of significant Hi-C contacts') support using an FDR threshold to define significant contacts, but specify FDR < 1 × 10⁻⁶, not 1 × 10⁻⁵. The Results ('Identification of Frequently Interacting Regions') discuss variation between samples, but do not describe the citing authors’ cell-line-specific modification. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA strong signal for distal chromatin interactions in bulk genomic assays such as Hi-C is associated with tissue-specific, presumably enhancer-dependent, expression.
“Furthermore, a strong signal for distal chromatin interactions in bulk genomic assays such as Hi-C is associated with tissue-specific, presumably enhancer-dependent, expression152.”
From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [152]
FUMA contains Hi-C data for 14 tissue types from the study of Schmitt et al.
“FUMA currently contains Hi-C data for 14 tissue types from the study of Schmitt et al. 51 .”
From Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence (2018) · cites this paper as [51]
The HAR202-Npas3 promoter interaction was not observed in Hi-C experiments from adult human dorsolateral prefrontal cortex or developing human cerebral cortex at mid-gestation.
“In contrast, this interaction was not observed in Hi-C experiments performed in cells neither from adult human dorsolateral prefrontal cortex (Schmitt et al. 2016; supplementary fig. S9, Supplementary Material online) nor from developing human cerebral cortex at mid-gestation (Won et al. 2016; supplementary fig. S10, Supplementary Material online).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Schmitt et al. 2016
The Results section, “A compendium of chromatin organization maps across 21 human cell and tissue types” (page unavailable), reports Hi-C analysis of human tissues, and the tissue-specific FIREs section mentions cortex data. But searches for HAR202, NPAS3, and dorsolateral prefrontal cortex found no passage assessing whether the HAR202–NPAS3 promoter interaction was observed. The mid-gestation claim is attributed to Won et al., not to this source. (LLM, conf=0.74)
Experimental — accuracy not yet measuredThe published Mb-scale TAD calls from Schmitt et al. (2016) were generated using an independent study and an independent TAD calling method.
“We used these published Mb-scale TAD calls in Figure S2 because Ren and colleagues used an independent study and an independent TAD calling method to compare TADs across H1 ES cell (Human H1) and H1 ESC-derived lineages—mesendoderm (MES), mesenchymal stem cells (MSC), neural progenitor cells (NPC), and trophoblast-like cells (TRO).”
From Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries (2018) · cites this paper as Schmitt et al., 2016
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- Authors
- Schmitt, A. D., Hu, M., Jung, I., Xu, Z., Qiu, Y., Tan, C. L., Li, Y., Lin, S., Lin, Y., Barr, C. L., & Ren, B.
- Affiliations
- University of California San Diego (US)
- New York University (US)
- Ludwig Cancer Research (US)
- University of North Carolina at Chapel Hill (US)
- University of Washington (US)
- Washington University in St. Louis (US)
- University Health Network (CA)
- Corresponding author
- Hu, Ming
- Ren, Bing
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 17
- Issue
- 8
- Pages
- 2042-2059
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5478386
- OpenAlex
- W2557097554
- Cited by
- 866
- References
- 52
- Citations by year
- 2026: 46 · 2025: 67 · 2024: 85 · 2023: 82 · 2022: 96 · 2021: 131 · 2020: 114 · 2019: 103 · 2018: 94 · 2017: 42 · 2016: 3
- FWCI
- 41.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Lincoln (University of Nebraska) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Ludwig Institute for Cancer Research
- NIH (U54DK107977, R01 ES024984, T32 GM008666, R01HG006292, R01HL129132)
- The Ontario Mental Health Foundation
- The Krembil Foundation
- The Hospital for Sick Children Psychiatric Endowment Fund
- 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 › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- chromatin contact maps, 3D genome organization, topologically associating domains, super-enhancers, CTCF, cohesin, non-coding variants, human tissue, chromosome conformation capture
- MeSH terms
- Cohesins, Adult, Animals, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Disease, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Nucleic Acid Conformation, Organ Specificity, Genome, Human, Conserved Sequence, Cell Cycle Proteins, Polymorphism, Single Nucleotide, Insulator Elements, Mice, Genome-Wide Association Study
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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