Abstract: Precise regulation of the embryonic stem cell (ESC) cycle is essential for self-renewal and differentiation. ESCs exhibit a distinct cell cycle structure from that of somatic cells and it varies depending on culture conditions. However, the epigenetic mechanisms governing ESC cell cycle regulation remain unclear. In this study, we demonstrate that the ATP-dependent chromatin remodeler Ino80 regulates cell cycle genes in primed ESCs. Loss of Ino80 significantly prolonged G1-phase in ESCs grown under primed conditions. Mechanistically, Ino80 directly binds to transcription start sites, modulating the expression of cell cycle-related genes. Additionally, Ino80 depletion induced cell apoptosis, highlighting its role in ESC survival. Interestingly, the regulatory function of Ino80 differs in differentiating ESCs, where its loss led to an extended S-phase. RNA-seq analysis revealed persistent dysregulation of genes associated with organ development and the cell cycle in differentiating Ino80 knockout ESCs, suggesting that Ino80’s function extends beyond undifferentiated ESCs. Overall, our findings establish Ino80 as a key transcriptional regulator of the ESC cell cycle and suggest its role may be broadly relevant to other cell types.
Funding Source: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT)(RS-2024-00344340).
