Identification of the common mechanism of zygotic genome activation in humans using early rat embryos

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15700
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kyoto University
• Principal Investigator: Morita Kohtaro 京都大学, 医学研究科, 特定助教 (80826545)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胚性ゲノム活性化 / ラット / マウス / エピゲノム

Outline of Final Research Achievements

RNA-Seq of early rat embryos showed that transcriptional transcripts change significantly between the 2- and 4-cell stages. Therefore, to investigate the transcription mechanism at the 2-cell stage, genes with high expression levels at the 2-cell stage were examined, and Brdt, a chaperone of H3K27ac involved in transcriptional activity, was detected at the top rank of the list. In addition, H3K27ac was massively altered at the time of transcriptional activation. Therefore, overexpression of Brdt resulted in an increase in 5-EU signalling at the 2-cell stage. As Brdt is transiently up-regulated in fertilised eggs and markedly down-regulated at the 2-cell stage in mice, the expression pattern of Brdt is different in mice and rats, suggesting that it may also play an important role in the timing of embryonic genome activation.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

マウスの胚性ゲノム活性化機構は2細胞期で生じ、ラットやヒトなどと異なる。胚性ゲノムの活性化は全能性獲得に必須とされ、このタイミングを制御する分子機構の解明は重要である。本研究では、胚性ゲノム活性化のタイミングの制御に関与していると考えられるBrdtの同定に成功した。本研究は、マウス以外の4～8細胞期で胚性ゲノムが活性化する分子機構とそのタイミングが異なる生物学的意義を解明する糸口になると考えられる。今後の発展として、胚の初期化機構の解明や繁殖技術の向上に貢献すると考えられる。