Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner
Alharbi, Adel B., Schmitz, Ulf, Marshall, Amy D., Vanichkina, Darya, Nagarajah, Rajini, Vellozzi, Melissa, Wong, Justin J.L., Bailey, Charles G., and Rasko, John E.J. (2020) Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner. RNA Biology, 18 (1). pp. 93-103.
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Abstract
CTCF is a master regulator of gene transcription and chromatin organisation with occupancy at thousands of DNA target sites genome-wide. While CTCF is essential for cell survival, CTCF haploinsufficiency is associated with tumour development and hypermethylation. Increasing evidence demonstrates CTCF as a key player in several mechanisms regulating alternative splicing (AS), however, the genome-wide impact of Ctcf dosage on AS has not been investigated.
We examined the effect of Ctcf haploinsufficiency on gene expression and AS in five tissues from Ctcf hemizygous (Ctcf+/-) mice. Reduced Ctcf levels caused distinct tissue-specific differences in gene expression and AS in all tissues. An increase in intron retention (IR) was observed in Ctcf+/- liver and kidney. In liver, this specifically impacted genes associated with cytoskeletal organisation, splicing and metabolism. Strikingly, most differentially retained introns were short, with a high GC content and enriched in Ctcf binding sites in their proximal upstream genomic region. This study provides new insights into the effects of CTCF haploinsufficiency on organ transcriptomes and the role of CTCF in AS regulation.
| Item ID: | 68971 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1555-8584 |
| Keywords: | Alternative splicing; CTCF; exon skipping; gene expression; haploinsufficiency; intron retention |
| Copyright Information: | © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
| Date Deposited: | 31 Aug 2021 01:12 |
| FoR Codes: | 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310504 Epigenetics (incl. genome methylation and epigenomics) @ 30% 31 BIOLOGICAL SCIENCES > 3105 Genetics > 310505 Gene expression (incl. microarray and other genome-wide approaches) @ 40% 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 30% |
| SEO Codes: | 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100% |
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