Head-to-head Antisense Transcription and R-loop Formation Promotes Transcriptional Activation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2015 Apr 23

PMID 25902512

Citations 129

Authors

Raquel Boque-Sastre

Marta Soler

Cristina Oliveira-Mateos

Anna Portela

Catia Moutinho

Sergi Sayols

Alberto Villanueva

Manel Esteller

Sonia Guil

Affiliations

Soon will be listed here.

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.

Citing Articles

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