A search for target genes of aberrant histone methylation diseases and the establishment of drug discovery platform based on elucidation of pathological conditions

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670169
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: Saga University
• Principal Investigator: Soejima Hidenobu 佐賀大学, 医学部, 教授 (30304885)
• Co-Investigator(Renkei-kenkyūsha): MATSUMOTO Naomichi 横浜市立大学, 大学院医学研究科, 教授 (80325638) ; YOSHIURA Ko-ichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
• Research Collaborator: HIGASHIMOTO Ken 佐賀大学, 医学部, 助教 (30304885) ; YATSUKI Hitomi 佐賀大学, 医学部, 技術専門職員 ; WATANABE Hidetaka 佐賀大学, 大学院・医学系研究科, 大学院生
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒストンメチル化酵素 / DNAメチル化 / ソトス症候群 / ゲノムインプリンティング

Outline of Final Research Achievements

We screened methylation status of imprinting associated differentially methylated regions (DMRs) in patients with Sotos syndrome, an aberrant histone methylation disease, to find NSD1 target genes and elucidate pathological conditions. We found two DMRs reduced methylation in about half of patients. Cells cultured with 5-Aza-CdR revealed the increased expression of imprinted genes with the reduced methylation of the DMRs. It was suggested that NSD1 mutations induced hypomethylation of the DMRs followed by the increased expression of the imprinted genes. Aberrant expression of the genes were probably involved in the pathological conditions of Sotos syndrome. In addition, we established the cell lines, which expressed FLAG tagged NSD1 protein. We plan to identify the NSD1 target genes using the cell lines.

Free Research Field

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