Effect of ATRX and G‐Quadruplex Formation by the VNTR Sequence on α‐Globin Gene Expression |
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| Authors: | Yue Li Dr. Junetha Syed Dr. Yuki Suzuki Sefan Asamitsu Dr. Norifumi Shioda Dr. Takahito Wada Prof. Hiroshi Sugiyama |
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| Affiliation: | 1. Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto, Japan;2. Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan;3. Department of Medical Ethics and Medical Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan;4. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan |
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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. |
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| Keywords: | alpha-globin gene ATR-X syndrome ATRX G-quadruplex VNTR sequence |
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