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Many facades of CTCF unified by its coding for three-dimensional genome architecture

本站小编 Free考研考试/2022-01-01

Qiang Wu,
Peifeng Liu1,
Leyang Wang1
MOE Key Lab of Systems Biomedicine, State Key Laboratory of Oncogenes and Related Genes, Center for Comparative Biomedicine, Institute of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University (SJTU), Shanghai, 200240, China

More InformationCorresponding author: E-mail address: qwu123@gmail.com (Qiang Wu)
Publish Date:2020-08-25




Abstract
CCCTC-binding factor (CTCF) is a multifunctional zinc finger protein that is conserved in metazoan species. CTCF is consistently found to play an important role in many diverse biological processes. CTCF/cohesin-mediated active chromatin ‘loop extrusion’ architects three-dimensional (3D) genome folding. The 3D architectural role of CTCF underlies its multifarious functions, including developmental regulation of gene expression, protocadherin (Pcdh) promoter choice in the nervous system, immunoglobulin (Ig) and T-cell receptor (Tcr) V(D)J recombination in the immune system, homeobox (Hox) gene control during limb development, as well as many other aspects of biology. Here, we review the pleiotropic functions of CTCF from the perspective of its essential role in 3D genome architecture and topological promoter/enhancer selection. We envision the 3D genome as an enormous complex architecture, with tens of thousands of CTCF sites as connecting nodes?and CTCF proteins as mysterious bonds that glue together genomic building parts with distinct articulation joints. In particular, we focus on the internal mechanisms by which CTCF controls higher order chromatin structures that manifest its many fa?ades of physiological and pathological functions. We also discuss the dichotomic role of CTCF sites as intriguing 3D genome nodes for seemingly contradictory ‘looping bridges’ and ‘topological insulators’ to frame a beautiful magnificent house for a cell's nuclear home.
Keywords: CTCF,
3D genome,
Loop extrusion,
Distal enhancer,
Target promoter,
Topological insulator



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http://www.jgenetgenomics.org/article/exportPdf?id=8025f5de-c988-42ad-83f6-4a3638f95083&language=en
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