医学研究科 キウイリオン フィオナ ソフィア マリア

SMARCA4-Mediated Regulation of Endogenous Retroviral Elements during Preimplantation Development

During preimplantation development, rapid epigenetic changes occur, and key transcription factors, such as “double homeobox” (DUX), drive zygotic genome activation (ZGA) in 2-cell embryos. The ATP-dependent chromatin remodeler SMARCA4 plays a crucial role, as its deletion leads to a two-cell arrest, emphasizing its importance in the 2-cell stage. My research ia focussed on the chromatin remodeler SMARCA4 and its interaction with DUX, impacting the upregulation of 2C-genes and DUX in 2-cell-like cells (2CLCs). Additionally, I seek to deepen our understanding of how SMARCA4 and DUX collaborate to regulate totipotent gene expression, focusing on the significant 2-cell stage. I hypothesize that SMARCA4 is responsible for opening the chromatin to activate master regulators such as DUX or OBOX4. This activation is proposed to involve a subsequent interaction of SMARCA4 with DUX, facilitating the accessibility of 2C-genes like Zscan4 and MERVL for transcription.