CTCF mediates chromatin looping via N-terminal domain-dependent cohesin retention

Elena M. Pugacheva, Naoki Kubo, Dmitri Loukinov, Md Tajmul, Sungyun Kang, Alexander L. Kovalchuk, Alexander V. Strunnikov, Gabriel E. Zentner, Bing Ren, Victor V. Lobanenkov

Research output: Contribution to journalArticlepeer-review

Abstract

The DNA-binding protein CCCTC-binding factor (CTCF) and the cohesin complex function together to shape chromatin architecture in mammalian cells, but the molecular details of this process remain unclear. Here, we demonstrate that a 79-aa region within the CTCF N terminus is essential for cohesin positioning at CTCF binding sites and chromatin loop formation. However, the N terminus of CTCF fused to artificial zinc fingers was not sufficient to redirect cohesin to non-CTCF binding sites, indicating a lack of an autonomously functioning domain in CTCF responsible for cohesin positioning. BORIS (CTCFL), a germline-specific paralog of CTCF, was unable to anchor cohesin to CTCF DNA binding sites. Furthermore, CTCF-BORIS chimeric constructs provided evidence that, besides the N terminus of CTCF, the first two CTCF zinc fingers, and likely the 3D geometry of CTCF-DNA complexes, are also involved in cohesin retention. Based on this knowledge, we were able to convert BORIS into CTCF with respect to cohesin positioning, thus providing additional molecular details of the ability of CTCF to retain cohesin. Taken together, our data provide insight into the process by which DNA-bound CTCF constrains cohesin movement to shape spatiotemporal genome organization.

Original languageEnglish
Pages (from-to)2020-2031
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number4
DOIs
Publication statusPublished - Jan 28 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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