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RFX5 as a regulator of spatial chromatin contacts and gene expression
Xiao Ge1, Yijun Zhang2, Yiru Han1,3
1Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, China.
Communications Biology
|May 23, 2026
Summary
The study identifies RFX5 as a novel regulator of three-dimensional (3D) genome organization, crucial for gene regulation in cancer. Loss of RFX5 disrupts chromatin looping and gene expression, impacting cancer-associated genes.
Area of Science:
- Genomics
- Molecular Biology
- Epigenetics
Background:
- Three-dimensional chromatin architecture is vital for gene regulation.
- Factors beyond CTCF and cohesin influencing chromatin organization are poorly understood.
Purpose of the Study:
- To identify novel regulators of chromatin organization.
- To investigate the role of RFX5 in 3D genome structure and gene regulation.
Main Methods:
- CRISPR-mediated RFX5 knockout in A375 cells.
- RNA-seq, ChIP-seq, ATAC-seq, QHR-4C, and Hi-C analyses were performed.
Main Results:
- RFX5 binds promoters/enhancers, co-localizes with CTCF/RAD21/H3K27ac, and maintains chromatin accessibility and loop strength.
- RFX5 deletion alters ~2,000 gene expressions, suppressing cancer-associated genes and oncogenic pathways.
- RFX5 acts as an insulator, balancing chromatin looping and affecting enhancer-promoter contacts.
Conclusions:
- RFX5 is a key architectural factor linking 3D genome structure to transcriptional programs in cancer and immunity.
- RFX5 plays a critical role in maintaining genome stability and regulating gene expression relevant to cancer development.
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