CTCF Mediates the Cis-Regulatory Hubs in Mouse Hearts
The 3D chromatin architecture establishes a complex network of genes and regulatory elements necessary for transcriptomic regulation in development and disease. This network can be modeled by cis-regulatory hubs (CRH), which underscore the local functional interactions between enhancers and promoter regions and differ from other higher-order chromatin structures such as topologically associated domains (TAD). The activity-by-contact (ABC) model of enhancer-promoter regulation has been recently used in the identification of these CRHs, but little is known about the role of transcription factor CCTC binding factor (CTCF) on ABC scores and their consequent impact on CRHs. Here, we show that the loss of CTCF leads to a reorganization of the ABC-derived rankings of putative enhancers in the mouse heart, a global reduction in the total number of CRHs and an increase in the size of CRHs. Furthermore, CTCF loss leads to a higher percentage of CRHs that cross TAD boundaries. These results provide additional evidence to support the importance of CTCF in forming the regulatory networks necessary for gene regulation.
Authors
- Dominic Paul Lee (ORCID: https://orcid.org/0000-0001-6880-453X)
- Alexandre Bureau (ORCID: https://orcid.org/0000-0001-8220-9999)
- Yee Phong Lim
- Cory C. Padilla
- Chukwuemeka George Anene-Nzelu (ORCID: https://orcid.org/0000-0003-4973-418X)
- Loïc Mangnier (ORCID: https://orcid.org/0000-0002-6394-9040)
- Ching Kit Chen (ORCID: https://orcid.org/0000-0003-4302-3539)
- Chang Jie Mick Lee (ORCID: https://orcid.org/0000-0001-6673-9391)
- Louis Hanqiang Gan (ORCID: https://orcid.org/0000-0002-1537-5441)
- Steve Bilodeau (ORCID: https://orcid.org/0000-0002-9799-3832)
- Wilson Lek Wen Tan (ORCID: https://orcid.org/0000-0002-5054-8512)
- Roger Foo (ORCID: https://orcid.org/0000-0002-8079-4618)
- Peter Yiqing Li
- Yan Zhu (ORCID: https://orcid.org/0000-0002-3933-5583)
- Rina Miao Qin Wang
- Wen Hao Zheng
Institutions
- Agency for Science, Technology and Research (SG)
- National University of Singapore (SG)
- Montreal Heart Institute (CA)
- Khoo Teck Puat Hospital (SG)
- ET Enterprises (United Kingdom) (GB)
- Centre hospitalier universitaire de Québec (CA)
- Université Laval (CA)
- Genome Institute of Singapore (SG)
- Université de Montréal (CA)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-10-09
- DOI
- https://doi.org/10.3390/ijms26199834
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Compute Canada
- National University of Singapore
- Institut de Cardiologie de Montréal
- Medical Research Council
- National Medical Research Council