Transcriptional complex and target genes during myocardial differentiation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Watanabe Yusuke 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (20562333)
• Co-Investigator(Kenkyū-buntansha): 中川 修 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40283593)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 二次心臓形成領域 / 転写調節 / Islet1

Outline of Final Research Achievements

Islet1 is a key transcription factor for the second heart field development. In this study, we aimed to identify interacting proteins of Islet1 to understand molecular mechanism of Islet1 transcriptional activity. First, we succeeded to establish epitope-tag fused Islet1 knock-in mouse lines, which recapitulated endogenous Islet1 expression pattern. Second, immunoprecipitation of Islet1 with anti-epitope tag antibodies from the knock-in mouse embryonic lysates followed by mass-spectrometry identified several candidates of Islet1-interacting proteins. Among them, Ldb1, Ssbp2 and Ssbp3, which are known Islet1 and Ldb1-binding proteins, respectively, were listed. Co-immunoprecipitation assay also verified the interaction between Islet1, Ldb1, Ssbp2 and Ssbp3. During myocardial differentiation from the second heart field, Islet1 possibly interacts with those factors to regulate its transcriptional activity for target gene expression.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

二次心臓形成領域は心筋、平滑筋、血管内皮細胞への分化能を持つ心血管前駆細胞を含む。また、二次心臓形成領域の発生異常に関連する先天性心疾患は約30％を占める。以上のことから二次心臓形成領域発生の分子的な理解は重要である。本研究成果で得られた二次心臓形成領域発生における必須転写因子であるIslet1の相互作用因子の同定は、Islet1の転写活性および遺伝子発現制御機構を分子的に理解することに貢献する。さらに将来的には、in vitroでの効率的な心筋作製や、先天性心疾患の原因究明に役立つ可能性も含む上で意義がある。