Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner

Ctcf haploinsufficiency mediates intron retention in a tissue-specific manner.

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Item Type: Article
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: Computational BioMedicine
Epigenetics and RNA Biology
Gene and Stem Cell Therapy
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: 03 Jan 2021 23:53
URI: https://eprints.centenary.org.au/id/eprint/833

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