Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells

TLDR

The 2 m of DNA must be folded into loops and domains to fit in the nucleus, and this 3D organization is essential for genome function, yet the protein factors that establish it remain unclear. The study investigates the roles of cohesin and CTCF in DNA loop formation. The authors analyze genome‑wide DNA contacts after depletion of cohesin and CTCF. CTCF is required to separate neighboring folding domains and retain cohesin, while cohesin shapes the domains, leading to distinct changes in gene expression.

Abstract

Significance For the 2m DNA to fit into the tiny cell nucleus, it is wrapped around nucleosomes and folded into loops clustering together in domains. Genome function depends on this 3D-organization, especially on-going dynamic processes like transcription. Techniques studying the network of DNA contacts genome-wide have recently revealed this 3D architecture, but the protein factors behind this are not understood. We study two proteins that are known to help form DNA loops: cohesin and CTCC-binding factor (CTCF). Respective depletion and analysis of DNA contacts genome-wide show that CTCF is required to separate neighboring folding domains and keep cohesin in place, whereas cohesin is important for shaping the domains. Consistently, we observe different changes of gene expression.