Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner.
Full text not available from this repository.Item Type: | Article |
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Status: | Published |
Official URL: | https://doi.org/10.1080/15476286.2020.1796052 |
Journal or Publication Title: | RNA Biology |
Page Range: | pp. 1-11 |
Date: | 2020 |
Divisions: | Gene and Stem Cell Therapy Epigenetics and RNA Biology Computational BioMedicine Cancer and Gene Regulation |
Depositing User: | General Admin |
Identification Number: | 10.1080/15476286.2020.1796052 |
ISSN: | 1547-6286 |
Date Deposited: | 03 Jan 2021 23:53 |
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. |
Creators: | Creators Email Alharbi, Adel B UNSPECIFIED Schmitz, Ulf UNSPECIFIED Marshall, Amy D UNSPECIFIED Vanichkina, Darya UNSPECIFIED Nagarajah, Rajini UNSPECIFIED Vellozzi, Melissa UNSPECIFIED Wong, Justin JL UNSPECIFIED Bailey, Charles G UNSPECIFIED Rasko, John EJ UNSPECIFIED |
Last Modified: | 12 Oct 2021 06:05 |
URI: | https://eprints.centenary.org.au/id/eprint/833 |
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