RFX5 as a regulator of spatial chromatin contacts and gene expression - PubMed
3 hours ago
- #Gene Regulation
- #Chromatin Architecture
- #RFX5
- RFX5 is identified as a novel regulator of chromatin organization, playing a key role in three-dimensional chromatin architecture and gene expression.
- In CRISPR-mediated RFX5 knockout A375 cells, RFX5 binds to promoters and enhancers, co-localizes with CTCF, RAD21, and H3K27ac, and helps maintain chromatin accessibility and loop strength.
- Deletion of RFX5 alters the expression of approximately 2,000 genes, strongly suppressing cancer-associated genes and oncogenic pathways, while reducing CTCF/RAD21 occupancy and promoter accessibility at downregulated genes.
- RFX5 functions as an insulator to balance chromatin looping: its absence weakens enhancer-promoter contacts at oncogenic loci but allows inappropriate long-range enhancer interactions at upregulated genes.
- Hi-C analysis shows that RFX5 deletion globally diminishes loop strength, with only mild effects on TAD insulation and compartmentalization, establishing RFX5 as a critical architectural factor linking 3D genome structure to transcriptional programs in cancer and immunity.