Oct motif variants in Beckwith–Wiedemann syndrome patients disrupt maintenance of the hypomethylated state of the H19/IGF2 imprinting control region

FEBS Letters

article

Shuichi Kubo¹  Chihiro Murata¹  Hanayo Okamura¹  Taku Sakasegawa¹  Chiye Sakurai¹  Kiyotaka Hatsuzawa¹  Naohiro Hori¹ 

[1] Division of Molecular Biology, Faculty of Medicine, School of Life Sciences, Tottori University

关键词: Beckwith–Wiedemann syndrome;    CTCF-binding site;    DNA demethylation;    imprinting control center 1;    Oct motif-dependent regulation;    P19 cell;   

DOI  :  10.1002/1873-3468.13750

来源: John Wiley & Sons Ltd.

【 摘 要 】

The methylation status of imprinting control center 1 (IC1) regulates the monoallelic transcription of H19 and Igf2 in mammalian cells. Several single nucleotide variants in Oct motifs within IC1 occur in patients with Beckwith– Wiedemann syndrome (BWS) who have hypermethylated maternal IC1. However, the importance of Oct motifs in the regulation of IC1 methylation status remains unclear. Here, we demonstrate that three variants found in BWS (BWS variants) suppress intensive induction of DNA demethylation, whereas consensus disruption of motifs unrelated to BWS only slightly affects the induction of demethylation. BWS variants reduce DNA demethylation levels and trigger the accumulation of DNA methylation downstream of the IC1 transgenes. Thus, the risk of IC1 hypermethylation is associated with inhibitory levels of Oct motif-dependent hypomethylation maintenance activities.

【 授权许可】

Unknown