ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters
Open accessAbstract
Chromatin interactions connect distal regulatory elements to target gene promoters guiding stimulus- and lineage-specific transcription. Few factors securing chromatin interactions have so far been identified. Here, by integrating chromatin interaction maps with the large collection of transcription factor-binding profiles provided by the ENCODE project, we demonstrate that the zinc-finger protein ZNF143 preferentially occupies anchors of chromatin interactions connecting promoters with distal regulatory elements. It binds directly to promoters and associates with lineage-specific chromatin interactions and gene expression. Silencing ZNF143 or modulating its DNA-binding affinity using single-nucleotide polymorphisms (SNPs) as a surrogate of site-directed mutagenesis reveals the sequence dependency of chromatin interactions at gene promoters. We also find that chromatin interactions alone do not regulate gene expression. Together, our results identify ZNF143 as a novel chromatin-looping factor that contributes to the architectural foundation of the genome by providing sequence specificity at promoters connected with distal regulatory elements. Chromatin interactions can connect distal regulatory elements to promoters via protein factors, but few such factors have been identified. Here, the authors show that zinc-finger protein ZNF143 is a sequence-specific chromatin-looping factor that connects promoters with distal regulatory elements.
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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 [363]
The Results sections on promoter binding and chromatin-interaction anchors report genome-wide promoter-associated ZNF143 binding and enrichment at anchors of promoter–distal regulatory-element interactions in human cell lines. They also link ZNF143 binding to cell-type-specific interactions. The study does not show this finding in mouse cells, so the human-and-mouse scope of the claim is not fully supported by this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredYY1 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 [363]
The Introduction and Discussion identify ZNF143 as a zinc-finger protein that binds a DNA recognition sequence and helps secure interactions between promoters and distal regulatory elements. The cited paper does not establish the corresponding claim about YY1; a search for YY1 found no relevant passage in our copy. Page numbers were not available. (LLM, conf=0.87)
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References 72 · Cited by 194
Research works printed but not linked: 59
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- Authors
- Bailey, S. D., Zhang, X., Desai, K., Aid, M., Corradin, O., Cowper-Sal·lari, R., Akhtar-Zaidi, B., Scacheri, P. C., Haibe-Kains, B., & Lupien, M.
- Affiliations
- University Health Network (CA)
- Dartmouth–Hitchcock Medical Center (US)
- Case Western Reserve University (US)
- Case Comprehensive Cancer Center (US)
- Ontario Institute for Cancer Research (CA)
- Corresponding author
- Lupien, Mathieu
- Venue
- Nature Communications
- Published
- 2015-02-03
- Volume
- 6
- Issue
- 1
- Pages
- 6186-6186
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4431651
- OpenAlex
- W2061412286
- Cited by
- 194
- References
- 72
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 16 · 2023: 11 · 2022: 22 · 2021: 20 · 2020: 28 · 2019: 19 · 2018: 14 · 2017: 26 · 2016: 19 · 2015: 8
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-04-10)
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Princess Margaret Cancer Foundation
- Ontario Institute for Cancer Research
- National Institutes of Health
- Canadian Institutes of Health Research
- National Cancer Institute (R01CA160356, R01CA155004)
- National Institute of General Medical Sciences (T32GM008056)
- 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 › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- ZNF143, chromatin looping, chromatin interactions, promoter, distal regulatory elements, zinc finger proteins, transcription factor binding, sequence specificity, chromatin structure, single nucleotide polymorphisms, gene expression regulation, lineage-specific gene expression
- MeSH terms
- Binding Sites, Chromatin, Humans, Promoter Regions, Genetic, Regulatory Sequences, Nucleic Acid, Trans-Activators, Polymorphism, Single Nucleotide
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