title: Head-to-head antisense transcription and R-loop formation promotes transcriptional activation.
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.
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Raquel
authors.initials: R
authors.lastname: Boque-Sastre
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Oliveira-Mateos
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Anna
authors.initials: A
authors.lastname: Portela
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Catia
authors.initials: C
authors.lastname: Moutinho
authors.affiliation: Cancer Epigenetics and Biology Program, and.
authors.forename: Sergi
authors.initials: S
authors.lastname: Sayols
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, L'Hospitalet, 08908 Barcelona, Catalonia, Spain;
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Cancer Epigenetics and Biology Program, and Department of Physiological Sciences II, School of Medicine, University of Barcelona, 08907 Barcelona, Catalonia, Spain; and Generalitat de Catalunya, Institucio Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Catalonia, Spain sguil@idibell.cat mesteller@idibell.cat.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Cancer Epigenetics and Biology Program, and sguil@idibell.cat mesteller@idibell.cat.
authors.forename: Sonia
authors.initials: S
authors.lastname: Guil
mesh_terms: D045744:Cell Line, Tumor; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014746:Vimentin / Q000235:genetics*
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D016376:Oligonucleotides, Antisense; D014746:Vimentin; D012313:RNA; D004247:DNA
keywords: DNA methylation; R loop; antisense transcription; nucleosome occupancy; vimentin