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

Yue Li, Junetha Syed, Yuki Suzuki, Sefan Asamitsu, Norifumi Shioda, Takahito Wada, Hiroshi Sugiyama

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)928-935
Number of pages8
JournalChemBioChem
Volume17
Issue number10
DOIs
Publication statusPublished - 2016 May 17
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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