ZNF143 mediates CTCF-bound promoter–enhancer loops required for murine hematopoietic stem and progenitor cell function
Open accessAbstract
CCCTC binding factor (CTCF) is an important factor in the maintenance of chromatin–chromatin interactions, yet the mechanism regulating its binding to chromatin is unknown. We demonstrate that zinc finger protein 143 (ZNF143) is a key regulator for CTCF-bound promoter–enhancer loops. In the murine genome, a large percentage of CTCF and ZNF143 DNA binding motifs are distributed 37 bp apart in the convergent orientation. Furthermore, deletion of ZNF143 leads to loss of CTCF binding on promoter and enhancer regions associated with gene expression changes. CTCF-bound promoter–enhancer loops are also disrupted after excision of ZNF143. ZNF143-CTCF-bound promoter–enhancer loops regulate gene expression patterns essential for maintenance of murine hematopoietic stem and progenitor cell integrity. Our data suggest a common feature of gene regulation is that ZNF143 is a critical factor for CTCF-bound promoter–enhancer loops.
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Long-term depletion of YY1 or ZNF143 in mammalian cells causes a significant reduction of enhancer-promoter loops, coupled with substantial changes in gene expression.
“Unlike CTCF and cohesin, long-term depletion of YY1 or ZNF143 in mammalian cells causes a significant reduction of enhancer–promoter loops, coupled with substantial changes in gene expression [295, 368, 369]”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [368]
The Results section on ZNF143 depletion reports significantly fewer promoter–enhancer loops in Znf143-deleted murine hematopoietic stem and progenitor cells; the Results section on regulated pathways reports significant gene-expression changes. This supports the ZNF143 portion of the multiply cited sentence, but this paper does not establish the stated long-term timescale or extend the finding beyond the murine cells studied. The YY1 portion is not attributed specifically to this source. (LLM, conf=0.83)
Experimental — accuracy not yet measuredZNF143 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 [368]
The Results (Fig. 2; page unavailable) show ZNF143 at promoter–enhancer loop anchors in murine hematopoietic stem and progenitor cells. This source does not establish the same finding in human cells or show that the loops are lineage-specific. The separate promoter-binding clause is cited to [367], not this source. (LLM, conf=0.85)
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Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
Narducci, D. N., & Hansen, A. S. (2025) · Molecular Cell · doi:10.1016/j.molcel.2024.11.032 · Cited by 25 · see citing works
- Authors
- Zhou, Q., Yu, M., Tirado-Magallanes, R., Li, B., Kong, L., Guo, M., Tan, Z. H., Lee, S., Chai, L., Numata, A., Benoukraf, T., Fullwood, M. J., Osato, M., Ren, B., & Tenen, D. G.
- Affiliations
- National University of Singapore (SG)
- Fudan University (CN)
- Ludwig Cancer Research (US)
- The University of Texas MD Anderson Cancer Center (US)
- Brigham and Women's Hospital (US)
- Kyushu University (JP)
- Memorial University of Newfoundland (CA)
- Agency for Science, Technology and Research (SG)
- University of California San Diego (US)
- Harvard University (US)
- Corresponding author
- Tenen, Daniel G.
- ORCID
- Venue
- Nature Communications
- Published
- 2021-01-04
- Volume
- 12
- Issue
- 1
- Pages
- 43-43
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7782510
- OpenAlex
- W3120635680
- Cited by
- 79
- References
- 14
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 9 · 2022: 29 · 2021: 7
- FWCI
- 4.94
- 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)
- National University of Singapore (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Funders
- National Research Foundation
- National Research Foundation Singapore
- National Institutes of Health (HL131477)
- Medical Research Council
- National Medical Research Council
- Japan Society for the Promotion of Science (18K08362, 19K07668)
- National Heart, Lung, and Blood Institute (P01HL131477)
- National Cancer Institute (R35CA197697)
- 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, CTCF, chromatin looping, hematopoietic stem cells, hematopoietic progenitor cells, zinc finger proteins, gene expression regulation, gene expression
- MeSH terms
- CCCTC-Binding Factor, Animals, DNA, Enhancer Elements, Genetic, Hematopoiesis, Hematopoietic Stem Cells, Mice, Inbred C57BL, Phenotype, Promoter Regions, Genetic, Protein Binding, Transcription, Genetic, Trans-Activators, Mice, Knockout, Mice, Protein Stability
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