Enhanced activities of OCT4 and SOX2 facilitates epigenetic reprogramming by modulating cell cycle

Fusing VP16 transcription activation domain with OCT4 and SOX2 (OvSvK) promoted the generation of induced pluripotency stem cells (iPSCs) by remodeling cell cycle and epigenetic modification. Multiomic analyses revealed that the other 80% upregulated genes experienced increase in H3K4me3 and decrease in H3K27me3 and were enriched with genes which undergo more intensive DNA demethylation during cell proliferation. Consistent results were obtained when siCcnd1, siCdkn2a and Ccne1 were screened out and used to mimic the cell cycle remodeling. In summary, these studies set up a correlation between epigenetic modification during cell cycle remodeling and cell fate conversion.

将VP16转录激活结构域与OCT4、SOX2融合（即OvSvK系统），可通过重塑细胞周期与表观遗传修饰，促进诱导多能干细胞（induced pluripotency stem cells，iPSCs）的生成。多组学分析显示，另有80%的上调基因存在H3K4me3水平升高、H3K27me3水平降低的特征，且富集于细胞增殖过程中发生更为剧烈DNA去甲基化的基因群体。通过筛选siCcnd1、siCdkn2a与Ccne1并用以模拟细胞周期重塑，获得了一致的实验结果。综上，本研究确立了细胞周期重塑过程中的表观遗传修饰与细胞命运转换之间的关联。