CTCF as a regulator of alternative splicing: new tricks for an old player

Alharbi, Adel B., Schmitz, Ulf, Bailey, Charles G., and Rasko, John E.J. (2021) CTCF as a regulator of alternative splicing: new tricks for an old player. Nucleic Acids Research. (In Press)

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Abstract

Three decades of research have established the CCCTC-binding factor (CTCF) as a ubiquitously expressed chromatin organizing factor and master regulator of gene expression. A new role for CTCF as a regulator of alternative splicing (AS) has now emerged. CTCF has been directly and indirectly linked to the modulation of AS at the individual transcript and at the transcriptome-wide level. The emerging role of CTCF-mediated regulation of AS involves diverse mechanisms; including transcriptional elongation, DNA methylation, chromatin architecture, histone modifications, and regulation of splicing factor expression and assembly. CTCF thereby appears to not only co-ordinate gene expression regulation but contributes to the modulation of transcriptomic complexity. In this review, we highlight previous discoveries regarding the role of CTCF in AS. In addition, we summarize detailed mechanisms by which CTCF mediates AS regulation. We propose opportunities for further research designed to examine the possible fate of CTCF-mediated alternatively spliced genes and associated biological consequences. CTCF has been widely acknowledged as the ‘master weaver of the genome’. Given its multiple connections, further characterization of CTCF’s emerging role in splicing regulation might extend its functional repertoire towards a ‘conductor of the splicing orchestra’.

Item ID: 68811
Item Type: Article (Research - C1)
ISSN: 1362-4962
Copyright Information: © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Funders: National Health and Medical Research Council (NHMRC), Tour de Cure (TdC), Cancer Council NSW (CC), Cure the Future (CtF), Cancer Institute New South Wales (CI NSW)
Projects and Grants: NHMRC Project grant 1128748, NHMRC Project grant 1128175, NHMRC Investigator grant 1177305, NHMRC Investigator grant 1196405, TdC Scott Canner Research Fellowship, CI NSW Early Career Researcher Fellowship
Date Deposited: 28 Jul 2021 04:31
FoR Codes: 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310504 Epigenetics (incl. genome methylation and epigenomics) @ 50%
31 BIOLOGICAL SCIENCES > 3105 Genetics > 310505 Gene expression (incl. microarray and other genome-wide approaches) @ 50%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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