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

• Li, Yue

  Department of Chemistry, Graduate School of Science, Kyoto University

• Syed, Junetha

  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

Abstract

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.

Journal

• ChemBioChem

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

  Wiley-VCH Verlag

Keywords

• alpha-globin gene
• ATR-X syndrome
• ATRX
• G-quadruplex
• VNTR sequence

Details

• CRID: 1050845760787605888
• NII Article ID: 120006460113
• ISSN: 14394227
• HANDLE: 2433/230878
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles