title: Remodeling of retrotransposon elements during epigenetic induction of adult visual cortical plasticity by HDAC inhibitors.
abstract: BACKGROUND
  The capacity for plasticity in the adult brain is limited by the anatomical traces laid down during early postnatal life. Removing certain molecular brakes, such as histone deacetylases (HDACs), has proven to be effective in recapitulating juvenile plasticity in the mature visual cortex (V1). We investigated the chromatin structure and transcriptional control by genome-wide sequencing of DNase I hypersensitive sites (DHSS) and cap analysis of gene expression (CAGE) libraries after HDAC inhibition by valproic acid (VPA) in adult V1.
  
  
  RESULTS
  We found that VPA reliably reactivates the critical period plasticity and induces a dramatic change of chromatin organization in V1 yielding significantly greater accessibility distant from promoters, including at enhancer regions. VPA also induces nucleosome eviction specifically from retrotransposon (in particular SINE) elements. The transiently accessible SINE elements overlap with transcription factor-binding sites of the Fox family. Mapping of transcription start site activity using CAGE revealed transcription of epigenetic and neural plasticity-regulating genes following VPA treatment, which may help to re-program the genomic landscape and reactivate plasticity in the adult cortex.
  
  
  CONCLUSIONS
  Treatment with HDAC inhibitors increases accessibility to enhancers and repetitive elements underlying brain-specific gene expression and reactivation of visual cortical plasticity.
authors.affiliation: Department of Biosciences and Nutrition, NOVUM, Karolinska Institutet, Stockholm, Sweden.|Genome Science Lab, RIKEN, Hirosawa, Wako-shi, Saitama 351-0198 Japan.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lennartsson
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.affiliation: Lab for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.|F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115 USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Alka
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Department of Biology and BRIC, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Noro
authors.affiliation: Lab for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.|F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115 USA.|Department of Pharmacology, National University of Singapore, 10 Medical Drive 05-34, Singapore, Singapore.
authors.forename: Judy
authors.initials: J
authors.lastname: Sng
authors.affiliation: Department of Biology and BRIC, The Bioinformatics Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.affiliation: Lab for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.|F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115 USA.|Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, MA 02138 USA.
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
keywords: Chromatin; DHSS; Enhancers; HDAC inhibitors; Retrotransposon elements; Visual cortex plasticity