title: Splicing of a non-coding antisense transcript controls LEF1 gene expression.
abstract: In this report we have analyzed the role of antisense transcription in the control of LEF1 transcription factor expression. A natural antisense transcript (NAT) is transcribed from a promoter present in the first intron of LEF1 gene and undergoes splicing in mesenchymal cells. Although this locus is silent in epithelial cells, and neither NAT transcript nor LEF1 mRNA are expressed, in cell lines with an intermediate epithelial-mesenchymal phenotype presenting low LEF1 expression, the NAT is synthesized and remains unprocessed. Contrarily to the spliced NAT, this unspliced NAT down-regulates the main LEF1 promoter activity and attenuates LEF1 mRNA transcription. Unspliced LEF1 NAT interacts with LEF1 promoter and facilitates PRC2 binding to the LEF1 promoter and trimethylation of lysine 27 in histone 3. Expression of the spliced form of LEF1 NAT in trans prevents the action of unspliced NAT by competing for interaction with the promoter. Thus, these results indicate that LEF1 gene expression is attenuated by an antisense non-coding RNA and that this NAT function is regulated by the balance between its spliced and unspliced forms.
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain UCL Cancer Institute, University College London, London, WC1E6BT, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Beltran
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors.forename: Estel
authors.initials: E
authors.lastname: Aparicio-Prat
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors.forename: Rocco
authors.initials: R
authors.lastname: Mazzolini
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Millanes-Romero
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Massó
authors.affiliation: UCL Cancer Institute, University College London, London, WC1E6BT, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Jenner
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
authors.forename: Víctor M
authors.initials: VM
authors.lastname: Díaz
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Peiró
authors.affiliation: Programa de Recerca en Càncer, Institut Hospital del Mar d'Investigacions Mèdiques, 08003 Barcelona, Spain Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain agarcia@imim.es.
authors.forename: Antonio García
authors.initials: AG
authors.lastname: de Herreros
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D016372:RNA, Antisense / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D051821:Lymphoid Enhancer-Binding Factor 1; D016372:RNA, Antisense; D063151:Polycomb Repressive Complex 2