title: Regulating retrotransposon activity through the use of alternative transcription start sites.
abstract: Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Jenna
authors.initials: J
authors.lastname: Persson
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Babett
authors.initials: B
authors.lastname: Steglich
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
authors.forename: Agata
authors.initials: A
authors.lastname: Smialowska
authors.affiliation: Department of Biology, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Boyd
authors.affiliation: Department of Biology, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jette
authors.initials: J
authors.lastname: Bornholdt
authors.affiliation: Department of Biology, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Unite Dynamique du Génome, Département Génomes et Génétique, Pasteur Institute, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Schurra
authors.affiliation: Unite Dynamique du Génome, Département Génomes et Génétique, Pasteur Institute, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Arcangioli
authors.affiliation: Department of Biology, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.affiliation: Department of Biology, Cell Cycle and Genome Stability Group, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Olaf
authors.initials: O
authors.lastname: Nielsen
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden karl.ekwall@ki.se.
authors.forename: Karl
authors.initials: K
authors.lastname: Ekwall
mesh_terms: D001483:Base Sequence; D002384:Catalysis; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D008954:Models, Biological; D009154:Mutation; D009707:Nucleosomes; D010641:Phenotype; D018626:Retroelements; D013312:Stress, Physiological; D020079:Terminal Repeat Sequences; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D018626:Retroelements
keywords: chromatin remodeling; retrotransposable elements; transcriptional regulation