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Effect of ATRX and G‐Quadruplex Formation by the VNTR Sequence on α‐Globin Gene Expression
Author(s) -
Li Yue,
Syed Junetha,
Suzuki Yuki,
Asamitsu Sefan,
Shioda Norifumi,
Wada Takahito,
Sugiyama Hiroshi
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500655
Subject(s) - atrx , g quadruplex , gene , microbiology and biotechnology , biology , dna , promoter , globin , genetics , gene expression , mutation
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.