Institute of Cytology, Russian Academy of Sciences, 194064 St.-Petersburg, Russia.
Int J Mol Sci. 2023 Oct 21;24(20):15434. doi: 10.3390/ijms242015434.
The transcription factor Oct4 can rightfully be considered a pivotal element in maintaining pluripotency. In addition, its ability to function as a pioneer factor enables the reprogramming of somatic cells back into a pluripotent state. To better understand the regulation of the Oct4-encoding gene (), the main genetic elements that regulate its expression in different states of pluripotency ought to be identified. While some elements have been well characterized for their ability to drive expression, others have yet to be determined. In this work, we show that translocation of the gene fragment purported to span all essential -elements, including the well-known distal and proximal enhancers (DE and PE), into the locus impairs the self-renewal of mouse embryonic stem cells (ESCs) in the naïve pluripotency state, as well as their further advancement through the formative and primed pluripotency states, inducing overall differentiation failure. These results suggest that regulatory elements located outside the previously determined boundaries are critical for the proper spatiotemporal regulation of this gene during development, indicating the need for their better characterization.
转录因子 Oct4 可以被合理地视为维持多能性的关键因素。此外，它作为先驱因子的功能使体细胞能够重新编程为多能状态。为了更好地理解编码基因 (Oct4) 的调控，应该确定调节其在不同多能性状态下表达的主要遗传元件。虽然已经有一些元件因其驱动表达的能力而得到了很好的描述，但其他元件尚未确定。在这项工作中，我们表明，假定跨越所有必需元件的基因片段（包括著名的远端和近端增强子 (DE 和 PE)）易位到基因座会损害原始多能状态下的小鼠胚胎干细胞 (ESC) 的自我更新能力，以及它们通过形成和启动多能状态的进一步进展，导致整体分化失败。这些结果表明，位于先前确定的边界之外的调节元件对于该基因在发育过程中的适当时空调节至关重要，这表明需要更好地描述它们。
