title: Dioxin receptor and SLUG transcription factors regulate the insulator activity of B1 SINE retrotransposons via an RNA polymerase switch.
abstract: Complex genomes utilize insulators and boundary elements to help define spatial and temporal gene expression patterns. We report that a genome-wide B1 SINE (Short Interspersed Nuclear Element) retrotransposon (B1-X35S) has potent intrinsic insulator activity in cultured cells and live animals. This insulation is mediated by binding of the transcription factors dioxin receptor (AHR) and SLUG (SNAI2) to consensus elements present in the SINE. Transcription of B1-X35S is required for insulation. While basal insulator activity is maintained by RNA polymerase (Pol) III transcription, AHR-induced insulation involves release of Pol III and engagement of Pol II transcription on the same strand. B1-X35S insulation is also associated with enrichment of heterochromatin marks H3K9me3 and H3K27me3 downstream of B1-X35S, an effect that varies with cell type. B1-X35S binds parylated CTCF and, consistent with a chromatin barrier activity, its positioning between two adjacent genes correlates with their differential expression in mouse tissues. Hence, B1 SINE retrotransposons represent genome-wide insulators activated by transcription factors that respond to developmental, oncogenic, or toxicological stimuli.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain.
authors.forename: Angel Carlos
authors.initials: AC
authors.lastname: Román
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: González-Rico
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moltó
authors.forename: Henar
authors.initials: H
authors.lastname: Hernando
authors.forename: Ana
authors.initials: A
authors.lastname: Neto
authors.forename: Cristina
authors.initials: C
authors.lastname: Vicente-Garcia
authors.forename: Esteban
authors.initials: E
authors.lastname: Ballestar
authors.forename: José L
authors.initials: JL
authors.lastname: Gómez-Skarmeta
authors.forename: Jana
authors.initials: J
authors.lastname: Vavrova-Anderson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: White
authors.forename: Lluís
authors.initials: L
authors.lastname: Montoliu
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Fernández-Salguero
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D015870:Gene Expression; D005809:Genes, Regulator; D005819:Genetic Markers; D016678:Genome; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D038101:Insulator Elements / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D020086:Short Interspersed Nucleotide Elements / Q000235:genetics*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015027:Zebrafish
chemical_list: D005819:Genetic Markers; D006570:Heterochromatin; D018336:Receptors, Aryl Hydrocarbon; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D012319:RNA Polymerase II; D012320:RNA Polymerase III