CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Hansen, Anders S.
• Is Part Of: Nucleus. Volume 11: Issue 1(2020)
• Page Start: 132
• Page End: 148
• Publication Date: 2020-01-01
• Subjects: CTCF -- Cohesin -- TADs -- Loop Extrusion -- Convergent Rule -- Binding Polarity -- RNA-Binding Region -- PDS5 -- NIPBL; Cell nuclei -- Periodicals; Biology -- Periodicals; Biology; Cell nuclei; Periodicals; 571.6605
• DOI: 10.1080/19491034.2020.1782024
• Languages: English
• ISSNs: 1949-1034

Abstract

ABSTRACT: Mammalian genome structure is closely linked to function. At the scale of kilobases to megabases, CTCF and cohesin organize the genome into chromatin loops. Mechanistically, cohesin is proposed to extrude chromatin loops bidirectionally until it encounters occupied CTCF DNA-binding sites. Curiously, loops form predominantly between CTCF binding sites in a convergent orientation. How CTCF interacts with and blocks cohesin extrusion in an orientation-specific manner has remained a mechanistic mystery. Here, we review recent papers that have shed light on these processes and suggest a multi-step interaction between CTCF and cohesin. This interaction may first involve a pausing step, where CTCF halts cohesin extrusion, followed by a stabilization step of the CTCF-cohesin complex, resulting in a chromatin loop. Finally, we discuss our own recent studies on an internal RNA-Binding Region (RBRi) in CTCF to elucidate its role in regulating CTCF clustering, target search mechanisms and chromatin loop formation and future challenges.