Genetic analysis of mutations associated with polycomb repressive complex 2 in Weaver Syndrome

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06533
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Yokohama City University
• Principal Investigator: IMAGAWA Eri 横浜市立大学, 医学研究科, 博士研究員 (60579895)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: Weaver症候群 / ポリコーム蛋白質複合体2 / 全エクソーム解析

Outline of Final Research Achievements

In this study, we aimed to investigate a pathogenicity of a p.Arg236Thr in EED and a p.Glu610Val in SUZ12 , which was detected in a proband with clinically suspected Weaver Syndrome. The EED and SUZ12 proteins are components of polycomb repressive complex 2 (PRC2) that has histone methyltransferase activity and catalyzes the trimethylation of histone 3 at lysine 27 (H3K27me3). To investigate the functional effects of the mutations, we performed rescue experiments using the Tet-on system for 293 T-REx cells. The results showed that increased H3K27me3 signals were observed after wild-type EED or SUZ12 transfection, whereas the mutants failed to rescue and produced similar levels of H3K27me3 as the mock transfections. These results of reduced H3K27me3 levels indicate that the identified mutations might lead to PRC2 loss-of function. Finally, we summarized these results in the article on Human Mutation (Hum Mutat. 2017. Jun;38(6):637-648.) .

Free Research Field

遺伝学