title: Associations between nucleosome phasing, sequence asymmetry, and tissue-specific expression in a set of inbred Medaka species.
abstract: BACKGROUND
  Transcription start sites (TSSs) with pronounced and phased nucleosome arrays downstream and nucleosome-depleted regions upstream of TSSs are observed in various species.
  
  
  RESULTS
  We have characterized sequence variation and expression properties of this set of TSSs (which we call "Nucleocyclic TSSs") using germline and somatic cells of three medaka (Oryzias latipes) inbred isolates from different locations. We found nucleocyclic TSSs in medaka to be associated with higher gene expression and characterized by a clear boundary in sequence composition with potentially-nucleosome-destabilizing A/T-enrichment upstream (p < 10(-60)) and nucleosome- accommodating C/G-enrichment downstream (p < 10(-40)) that was highly conserved from an ancestor. A substantial genetic distance between the strains facilitated the in-depth analysis of patterns of fixed mutations, revealing a localization-specific equilibrium between the rates of distinct mutation categories that would serve to maintain the conserved sequence anisotropy around TSSs. Downstream of nucleocyclic TSSs, C to T, T to C, and other mutation rates on the sense strand increased around first nucleosome dyads and decreased around first linkers, which contrasted with genomewide mutational patterns around nucleosomes (p < 5 %). C to T rates are higher than G to A rates around nucleosome associated with germline nucleocyclic TSS sites (p < 5 %), potentially due to the asymmetric effect of transcription-coupled repair.
  
  
  CONCLUSIONS
  Our results demonstrate an atypical evolutionary process surrounding nucleocyclic TSSs.
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-0882, Japan. nakatani@cb.k.u-tokyo.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Department of Pathology, School of Medicine, Stanford University, Stanford, CA, 94305-5324, USA. cecilia.mello@gmail.com.
authors.forename: Cecilia C
authors.initials: CC
authors.lastname: Mello
authors.affiliation: Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-1192, Japan. hashimot@m.u-tokyo.ac.jp.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, 113-0033, Japan. kirita@biol.s.u-tokyo.ac.jp.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shimada
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, 113-0033, Japan. rynakamura@bs.s.u-tokyo.ac.jp.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, 113-0033, Japan. ttsuka@bs.s.u-tokyo.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-0882, Japan. quwei@cb.k.u-tokyo.ac.jp.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-0882, Japan. yoshimura@cb.k.u-tokyo.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshimura
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan. ysuzuki@k.u-tokyo.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan. ssugano@k.u-tokyo.ac.jp.
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, 113-0033, Japan. htakeda@biol.s.u-tokyo.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Departments of Pathology and Genetics, School of Medicine, Stanford University, Stanford, CA, 94305-5324, USA. afire@stanford.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Fire
authors.affiliation: Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, 277-0882, Japan. moris@cb.k.u-tokyo.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
mesh_terms: D000818:Animals; D019143:Evolution, Molecular; D007178:Inbreeding; D009707:Nucleosomes / Q000235:genetics*; D009928:Organ Specificity; D009990:Oryzias / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D024363:Transcription Initiation Site
chemical_list: D009707:Nucleosomes