title: Occupancy of tissue-specific cis-regulatory modules by Otx2 and TLE/Groucho for embryonic head specification.
abstract: Head specification by the head-selector gene, orthodenticle (otx), is highly conserved among bilaterian lineages. However, the molecular mechanisms by which Otx and other transcription factors (TFs) interact with the genome to direct head formation are largely unknown. Here we employ ChIP-seq and RNA-seq approaches in Xenopus tropicalis gastrulae and find that occupancy of the corepressor, TLE/Groucho, is a better indicator of tissue-specific cis-regulatory modules (CRMs) than the coactivator p300, during early embryonic stages. On the basis of TLE binding and comprehensive CRM profiling, we define two distinct types of Otx2- and TLE-occupied CRMs. Using these devices, Otx2 and other head organizer TFs (for example, Lim1/Lhx1 (activator) or Goosecoid (repressor)) are able to upregulate or downregulate a large battery of target genes in the head organizer. An underlying principle is that Otx marks target genes for head specification to be regulated positively or negatively by partner TFs through specific types of CRMs.
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Yasuoka
authors.affiliation: 1] Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8568, Japan [2] Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: 1] Division of Life Sciences, Komaba Organization for Educational Excellence, College of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan [2].
authors.forename: Shuji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Biological Sciences, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minamiohsawa, Hachiohji, Tokyo 192-0397, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Someya
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2].
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sudou
authors.affiliation: 1] Division of Life Sciences, Komaba Organization for Educational Excellence, College of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan [2] Research Center for Stem Cell Engineering (SCRC), National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba-shi, Ibaraki 305-8562, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Haramoto
authors.affiliation: Department of Developmental and Cell Biology, Developmental Biology Center, University of California, Irvine California 92697-2300, USA.
authors.forename: Ken W
authors.initials: KW
authors.lastname: Cho
authors.affiliation: 1] Research Center for Stem Cell Engineering (SCRC), National Institute of Advanced Industrial Science and Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba-shi, Ibaraki 305-8562, Japan [2] Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Asashima
authors.affiliation: 1] Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8568, Japan [2] Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.affiliation: Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Taira
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D005260:Female; D005775:Gastrula / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006257:Head / Q000196:embryology*; D008297:Male; D009928:Organ Specificity; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051857:Otx Transcription Factors; D014157:Transcription Factors; D029867:Xenopus Proteins; C497661:Otx2 protein, Xenopus; C108340:TLE1 protein, Xenopus