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

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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

Codes

  • NII Article ID (NAID)
    120006460113
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1439-4227
  • Data Source
    IR 
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