Effect of ATRX and G-Quadruplex Formation by the VNTR Sequence on α-Globin Gene Expression

HANDLE オープンアクセス
  • 朝光, 世煌
    Department of Chemistry, Graduate School of Science, Kyoto University
  • 杉山, 弘
    Department of Chemistry, Graduate School of Science, Kyoto University
  • Suzuki, Yuki
    Department of Chemistry, Graduate School of Science, Kyoto University
  • Asamitsu, Sefan
    Department of Chemistry, Graduate School of Science, Kyoto University
  • Shioda, Norifumi
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University
  • Wada, Takahito
    Department of Medical Ethics and Medical Genetics, Graduate School of Medicine, Kyoto University
  • Sugiyama, Hiroshi
    Department of Chemistry, Graduate School of Science, Kyoto University ・Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University

抄録

ATR-X (α-thalassemia/mental retardation X-linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence in the promoter region of the α-globin gene cluster. The VNTR sequence, which contains the potential G-quadruplex-forming sequence CGC(GGGGCGGGG)n, is involved in the downregulation of α-globin expression. We investigated G-quadruplex and i-motif formation in single-stranded DNA and long double-stranded DNA. The promoter region without the VNTR sequence showed approximately twofold higher luciferase activity than the promoter region harboring the VNTR sequence. G-quadruplex stabilizers hemin and TMPyP4 reduced the luciferase activity, whereas expression of ATRX led to a recovery in reporter activity. Our results demonstrate that stable G-quadruplex formation by the VNTR sequence downregulates the expression of α-globin genes and that ATRX might bind to and resolve the G-quadruplex.

収録刊行物

  • ChemBioChem

    ChemBioChem 17 (10), 928-935, 2016-05-17

    Wiley-VCH Verlag

キーワード

詳細情報 詳細情報について

  • CRID
    1050845760787605888
  • NII論文ID
    120006460113
  • ISSN
    14394227
  • HANDLE
    2433/230878
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB
    • CiNii Articles

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