A unified model of gene expression control by cohesin and CTCF

講演要旨

Cohesin- and CTCF-mediated chromatin looping is widely linked to enhancer-promoter communication and gene regulation, yet their scope in global gene activation remains debated. We demonstrate that cohesin and CTCF regulate hundreds of genes, but the magnitude of gene regulation is subtle. Cohesin promotes gene activation via CBP/p300-dependent enhancers, while CTCF anchors cohesin loops to guide enhancers to specific targets and prevent mistargeting. Beyond this architectural role, CTCF acts as a transcriptional activator and repressor of sense and anti-sense transcription, depending on its precise binding position and orientation in promoters. Promoter-bound CTCF activates housekeeping genes by promoting DNA accessibility and RNA polymerase II recruitment, explaining its universal essentiality in mammalian cells. CTCF’s transcriptional activation function—but not its loop-anchoring role—is shared with its vertebrate-specific paralog, CTCFL. These findings clarify the scope of cohesin and CTCF in global gene regulation and establish a unified model integrating their enhancer-dependent and -independent functions.