医学研究科 キウイリオン フィオナ ソフィア マリア

The Involvement and Importance of the ATP-dependent Chromatin Remodeler SMARCA4 for the 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.