Identification of regulatory factors for somatic imprinted DMR establishment and elucidation of their molecular mechanisms

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Saga University
• Principal Investigator: Soejima Hidenobu 佐賀大学, 医学部, 教授 (30304885)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 体細胞性インプリントＤＭＲ / DNAメチル化 / ゲノムインプリンティング

Outline of Final Research Achievements

We screened regulatory factors for somatic imprinted DMR establishment within Igf2r/Airn domain using shRNA libraries. We found six genes as candidates. Second-order analyses revealed two genes as putative regulatory factors for the somatic DMR establishment. In addition, we generated model mice, in which candidate regions for DMR establishment were deleted, to clarify a mechanism of DMR establishment within Kcnq1ot1/Cdkn1c domain. Since DMR methylation did not change in the model mice, it was suggested that the regulatory region for DMR establishment did not exist within the deleted region. However, it was suggested that at least the enhancer for Cdkn1c would be included within the deleted region because Cdkn1c expression decreased in the model mice.

Free Research Field

エピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

インプリント関連疾患では、配偶子形成過程で確立されるgDMRだけではなく、着床後に確立されるsDMRのメチル化も重要である。sDMRのメチル化を制御する因子の同定を目的に、Igf2r/Airn領域を対象に解析したところ、候補制御因子を２種類同定した。一方、Kcnq1ot1/Cdkn1c領域では、少なくともCdkn1cの候補エンハンサーの存在を突き止めた。インプリンティングの分子機構解明と疾患の病態解明に寄与する結果と考えられる。