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Updated: Jun 4, 2025
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CRISPR-Mediated Reorganization of Chromatin Loop Structure
Published on: September 14, 2018
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Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function
Domenic N Narducci1, Anders S Hansen1
1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
Molecular Cell
|December 21, 2024
Summary
The transcription factor ZNF143/ZFP143 does not generally regulate chromatin looping as previously thought. Instead, it is a stable promoter-binding factor essential for regulating mitochondrial and ribosomal genes.
Area of Science:
- Molecular Biology
- Genetics
- Epigenetics
Background:
- Distal regulatory elements like enhancers and promoters interact to control gene expression.
- Protein regulators of these chromatin interactions are largely unknown.
- ZNF143/ZFP143 was previously suspected to be a key regulator of chromatin looping, potentially with CTCF.
Purpose of the Study:
- To investigate the role of ZNF143/ZFP143 in chromatin looping.
- To determine the relationship between ZNF143/ZFP143 and CTCF in regulating chromatin interactions.
- To clarify the function of ZNF143/ZFP143 in gene regulation.
Main Methods:
- Utilized dual-purpose degron/imaging tags for CTCF and ZNF143/ZFP143.
- Assessed looping function and cross-effects combinatorially in mouse and human cells.
- Analyzed chromatin binding and dwell time of ZNF143/ZFP143.
Main Results:
- ZNF143/ZFP143 does not possess a general chromatin looping function.
- ZNF143/ZFP143 functions largely independently of CTCF.
- ZNF143/ZFP143 is a highly conserved, essential transcription factor binding proximal promoters with long chromatin dwell times (>20 min).
- ZNF143/ZFP143 regulates key mitochondrial and ribosomal genes.
Conclusions:
- The proposed role of ZNF143/ZFP143 as a general looping factor is refuted.
- ZNF143/ZFP143 is a crucial transcription factor for specific gene sets, particularly those involved in mitochondrial function and ribosome biogenesis.
- Its stable promoter association underlies its regulatory role.
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