title: CAGE-defined promoter regions of the genes implicated in Rett Syndrome.
abstract: BACKGROUND
  Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.
  
  
  RESULTS
  Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.
  
  
  CONCLUSIONS
  Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome.
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. mvitezic@gmail.com.|Department of Cell and Molecular Biology (CMB), Karolinska Institutet, Stockholm, Sweden. mvitezic@gmail.com.|The Bioinformatics Center, Department of Biology and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark. mvitezic@gmail.com.
authors.forename: Morana
authors.initials: M
authors.lastname: Vitezic
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. nicolas.bertin@gmail.com.|Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. nicolas.bertin@gmail.com.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. nicolas.bertin@gmail.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertin
authors.affiliation: The Bioinformatics Center, Department of Biology and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark. robin@binf.ku.dk.
authors.forename: Robin
authors.initials: R
authors.lastname: Andersson
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA. LLipovich@med.wayne.edu.|Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, USA. LLipovich@med.wayne.edu.
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. kawaji@gsc.riken.jp.|Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. kawaji@gsc.riken.jp.|RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), Wako, Japan. kawaji@gsc.riken.jp.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. timo.lassmann@telethonkids.org.au.|Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. timo.lassmann@telethonkids.org.au.|Telethon Kids Institute, The University of Western Australia, Perth, Australia. timo.lassmann@telethonkids.org.au.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: The Bioinformatics Center, Department of Biology and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark. albin@binf.ku.dk.
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.affiliation: Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. peter.heutink@dzne.de.|German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. peter.heutink@dzne.de.|Eberhard Karls University, Tübingen, Germany. peter.heutink@dzne.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Heutink
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Dept of Medical Genetics, University of British Columbia, Vancouver, Canada. dang@cmmt.ubc.ca.
authors.forename: Dan
authors.initials: D
authors.lastname: Goldowitz
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Dept of Medical Genetics, University of British Columbia, Vancouver, Canada. tjha@cmmt.ubc.ca.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ha
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Dept of Medical Genetics, University of British Columbia, Vancouver, Canada. pzhang@cmmt.ubc.ca.
authors.forename: Peter
authors.initials: P
authors.lastname: Zhang
authors.affiliation: FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. annarita.patrizi@childrens.harvard.edu.
authors.forename: Annarita
authors.initials: A
authors.lastname: Patrizi
authors.affiliation: FM Kirby Neurobiology Center, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. michela.fagiolini@childrens.harvard.edu.
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. forrest@gsc.riken.jp.|Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. forrest@gsc.riken.jp.
authors.forename: Alistair R R
authors.initials: AR
authors.lastname: Forrest
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. carninci@riken.jp.|Division of Genomic Technologies (DGT), RIKEN Center for Life Science Technologies, Yokohama, Japan. carninci@riken.jp.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: Omics Science Center, RIKEN Yokohama Institute, Omics Science Center (OSC), 1-17-22 Suehiro cho, Tsurumi ku, Yokohama, Japan. alka.saxena@gstt.nhs.uk.|Biomedical Research Centre at Guy's and St Thomas' Trust, Genomics Core Facility, Guy's Hospital, London, UK. alka.saxena@gstt.nhs.uk.
authors.forename: Alka
authors.initials: A
authors.lastname: Saxena
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics; D020869:Gene Expression Profiling; D023281:Genomics; D006657:Histones / Q000235:genetics; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics* / Q000473:pathology; D016385:TATA Box / Q000235:genetics; D024363:Transcription Initiation Site
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; D006657:Histones; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human