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Cited by 278Genomics and Chromatin DynamicsChromatin Remodeling and CancerCancer-related molecular mechanisms research

Genome-wide map of regulatory interactions in the human genome

Open access
Heidari, Nastaran, Phanstiel, Douglas H., He, Chao, Grubert, Fabian, Jahanbani, Fereshteh, Kasowski, Maya, Zhang, Michael Q., Snyder, Michael P.·2014·Genome Research
DOI 10.1101/gr.176586.114PMC PMC4248309
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Abstract

Increasing evidence suggests that interactions between regulatory genomic elements play an important role in regulating gene expression. We generated a genome-wide interaction map of regulatory elements in human cells (ENCODE tier 1 cells, K562, GM12878) using Chromatin Interaction Analysis by Paired-End Tag sequencing (ChIA-PET) experiments targeting six broadly distributed factors. Bound regions covered 80% of DNase I hypersensitive sites including 99.7% of TSS and 98% of enhancers. Correlating this map with ChIP-seq and RNA-seq data sets revealed cohesin, CTCF, and ZNF143 as key components of three-dimensional chromatin structure and revealed how the distal chromatin state affects gene transcription. Comparison of interactions between cell types revealed that enhancer–promoter interactions were highly cell-type-specific. Construction and comparison of distal and proximal regulatory networks revealed stark differences in structure and biological function. Proximal binding events are enriched at genes with housekeeping functions, while distal binding events interact with genes involved in dynamic biological processes including response to stimulus. This study reveals new mechanistic and functional insights into regulatory region organization in the nucleus.

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  • ZNF143 binds to promoters globally and is found at the anchors of many lineage-specific enhancer-promoter loops in human and mouse cells.

    “Meanwhile, ZNF143 binds to promoters globally [367] and was found at the anchors of many lineage-specific enhancer–promoter loops in human and mouse cells [362–364, 368].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [362]

    The Results section reports that ZNF143 is enriched at interacting loci and that enhancer–promoter interactions differ between two human cell lines. It does not establish that ZNF143 anchors the cell-type-specific enhancer–promoter loops specifically, and its own interaction map is of human, not mouse, cells. The separate promoter-binding clause is cited to [367], not this paper. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • YY1 and ZNF143 are zinc finger TFs with DNA binding domains that have been implicated as looping factors mediating interactions between active regulatory elements.

    “YY1 and ZNF143 are both zinc finger TFs with DNA binding domains that have recently been implicated as looping factors mediating interactions between active regulatory elements [295, 362–365].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [362]

    The Results section identifies ZNF143 as a zinc finger protein enriched at interacting loci, and the Discussion says the findings implicate it in long-range chromatin interactions. The passages do not establish the same claim for YY1, and the Discussion says ZNF143’s specific role in establishing or maintaining chromatin structure remains to be determined. No page numbers were available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Heidari, N., Phanstiel, D. H., He, C., Grubert, F., Jahanbani, F., Kasowski, M., Zhang, M. Q., & Snyder, M. P.
Affiliations
  • Stanford Medicine (US)
  • Tsinghua University (CN)
  • Yale University (US)
  • The University of Texas at Dallas (US)
Corresponding author
Snyder, Michael P.
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2014-09-16
Volume
24
Issue
12
Pages
1905-1917
ISSN
  • 1088-9051 (ISSN-L)
  • 1549-5469
DOI
10.1101/gr.176586.114
PMC
PMC4248309
OpenAlex
W2169710039
Cited by
278
References
52
Citations by year
2026: 6 · 2025: 8 · 2024: 17 · 2023: 19 · 2022: 18 · 2021: 18 · 2020: 31 · 2019: 25 · 2018: 24 · 2017: 41 · 2016: 36 · 2015: 31 · 2014: 4
Type
posted content
Language
en
Open access
Licence
cc-by
Locations
  • Genome Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • NIH (5U54HG00699602)
  • National Basic Research Program of China (2012CB316503)
  • National Natural Science Foundation of China (91019016)
  • Damon Runyon Cancer Research Foundation (DRG-2122-12)
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 › Cancer Research › Cancer-related molecular mechanisms research
Keywords
three-dimensional chromatin structure, enhancer-promoter interactions, DNase I hypersensitive sites, cohesin, CTCF, ZNF143, K562 cells, GM12878 cells, transcriptional regulation, ENCODE
MeSH terms
CCCTC-Binding Factor, Cohesins, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, Chromosome Mapping, Enhancer Elements, Genetic, Epistasis, Genetic, Gene Expression Regulation, Humans, Organ Specificity, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Transcription Factors, Trans-Activators, Genome, Human, Cluster Analysis, Cell Cycle Proteins, Computational Biology, Genomics, Chromatin Immunoprecipitation, Gene Regulatory Networks, Genome-Wide Association Study, Genetic Loci, Datasets as Topic

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