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Published on: March 31, 2019
Systematic screening of CTCF binding partners identifies that BHLHE40 regulates CTCF genome-wide distribution and
Gongcheng Hu1,2,3,4,5, Xiaotao Dong1,2,3,4,5, Shixin Gong1,2,3,4,5
1CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.
Insights
Researchers identified new factors that interact with CTCF to regulate chromatin loops. The study found that BHLHE40 specifically impacts CTCF loop formation by altering CTCF binding, revealing novel insights into gene regulation.
Area of Science:
- Genomics and Epigenetics
- Molecular Biology
- Chromatin Structure and Dynamics
Background:
- CCCTC-binding factor (CTCF) is crucial for organizing the 3D genome architecture through chromatin loops.
- While CTCF mediates these interactions, other co-localized factors are known to influence loop formation, but a comprehensive analysis is lacking.
Purpose of the Study:
- To systematically identify novel participants and regulators of CTCF-mediated chromatin loops.
- To investigate the functional roles of identified factors in CTCF loop formation and regulation.
Main Methods:
- Performed co-localization analysis between human super conserved CTCF (hscCTCF) binding sites and publicly available ChIP-seq data for various factors in humans.
- Integrated co-localization data with existing CTCF loop information to identify factors promoting loop formation.
- Conducted in-depth analysis of individual factors and specifically investigated the role of BHLHE40 in CTCF binding and loop regulation.
Main Results:
- Identified numerous novel factors that overlap with hscCTCF binding sites, suggesting potential roles in chromatin looping.
- Observed that clustered factors at CTCF binding sites are associated with the promotion of CTCF loops.
- Demonstrated that BHLHE40 directly influences CTCF loop formation by modulating CTCF binding to chromatin.
Conclusions:
- This study reveals a broad spectrum of factors with the potential to participate in or regulate CTCF loops.
- A novel function for BHLHE40 in modulating CTCF loop formation is discovered, highlighting its importance in 3D genome organization.
- The findings provide a foundation for understanding the complex regulatory network governing CTCF-mediated chromatin interactions.
Abstract:
CTCF plays a pivotal role in mediating chromatin interactions, but it does not do so alone. A number of factors have been reported to co-localize with CTCF and regulate CTCF loops, but no comprehensive analysis of binding partners has been performed. This prompted us to identify CTCF loop participants and regulators by co-localization analysis with CTCF. We screened all factors that had ChIP-seq data in humans by co-localization analysis with human super conserved CTCF (hscCTCF) binding sites, and identified many new factors that overlapped with hscCTCF binding sites. Combined with CTCF loop information, we observed that clustered factors could promote CTCF loops. After in-depth mining of each factor, we found that many factors might have the potential to promote CTCF loops. Our data further demonstrated that BHLHE40 affected CTCF loops by regulating CTCF binding. Together, this study revealed that many factors have the potential to participate in or regulate CTCF loops, and discovered a new role for BHLHE40 in modulating CTCF loop formation.
