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.
journal_name
Proc Natl Acad Sci U S Aauthors
Pugacheva EM,Kubo N,Loukinov D,Tajmul M,Kang S,Kovalchuk AL,Strunnikov AV,Zentner GE,Ren B,Lobanenkov VVdoi
10.1073/pnas.1911708117subject
Has Abstractpub_date
2020-01-28 00:00:00pages
2020-2031issue
4eissn
0027-8424issn
1091-6490pii
1911708117journal_volume
117pub_type
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