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

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.

authors

Pugacheva EM,Kubo N,Loukinov D,Tajmul M,Kang S,Kovalchuk AL,Strunnikov AV,Zentner GE,Ren B,Lobanenkov VV

doi

10.1073/pnas.1911708117

subject

Has Abstract

pub_date

2020-01-28 00:00:00

pages

2020-2031

issue

4

eissn

0027-8424

issn

1091-6490

pii

1911708117

journal_volume

117

pub_type

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