Head-to-head antisense transcription and R-loop formation promotes transcriptional activation

Boque Sastre, Raquel ORCID: https://orcid.org/0000-0002-0214-8848, Soler, Marta, Oliveira-Mateos, Cristina, Portela, Anna, Moutinho, Catia, Sayols, Sergi, Villanueva, Alberto, Esteller, Manel and Guil, Sonia 2015. Head-to-head antisense transcription and R-loop formation promotes transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 112 (18) , pp. 5785-5790. 10.1073/pnas.1421197112

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Abstract

The mechanisms used by antisense transcripts to regulate their corresponding sense mRNAs are not fully understood. Herein, we have addressed this issue for the vimentin (VIM) gene, a member of the intermediate filament family involved in cell and tissue integrity that is deregulated in different types of cancer. VIM mRNA levels are positively correlated with the expression of a previously uncharacterized head-to-head antisense transcript, both transcripts being silenced in colon primary tumors concomitant with promoter hypermethylation. Furthermore, antisense transcription promotes formation of an R-loop structure that can be disfavored in vitro and in vivo by ribonuclease H1 overexpression, resulting in VIM down-regulation. Antisense knockdown and R-loop destabilization both result in chromatin compaction around the VIM promoter and a reduction in the binding of transcriptional activators of the NF-κB pathway. These results are the first examples to our knowledge of R-loop–mediated enhancement of gene expression involving head-to-head antisense transcription at a cancer-related locus.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Date of First Compliant Deposit:	1 November 2019
Date of Acceptance:	2 April 2015
Last Modified:	06 May 2023 07:54
URI:	https://orca.cardiff.ac.uk/id/eprint/126474

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