Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states. A second wave of reconfiguration occurs just prior to pluripotency acquisition, where a majority of early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. Our comprehensive characterization of reprogramming-associated molecular changes broadens our understanding of this process and sheds light on how TFs access and change the chromatin during cell-fate transitions.

中文翻译：

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染色质和转录因子占用的暂时性和永久性重新配置驱动程序重新编程。

体细胞重编程为诱导性多能干细胞（iPSC）诱导了反映胚胎干细胞（ESC）状态的基因组结构变化。但是，只有极少数的细胞通常会转变为多能性，这限制了我们对过程的理解。在这里，我们通过重编程成为iPSC的中间体的分离亚群的时程分析来表征重编程过程中的DNA调控格局。重编程期间，染色质状态和转录因子（TF）的广泛重新配置发生了，并且无法重编程的细胞部分保留了其原始染色质状态。重新配置的第二波浪潮刚好在多能性获得之前发生，在这种情况下，大多数早期变化都恢复为体细胞状态，并且许多定义多能性状态的变化得以确立。我们对重编程相关分子变化的全面表征拓宽了我们对这一过程的理解，并阐明了TF在细胞命运转变过程中如何进入和改变染色质。