The Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel.
The Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Stem Cell Reports. 2017 Oct 10;9(4):1291-1303. doi: 10.1016/j.stemcr.2017.08.021. Epub 2017 Sep 28.
Embryonic stem cells (ESCs) are regulated by pluripotency-related transcription factors in concert with chromatin regulators. To identify additional stem cell regulators, we screened a library of endogenously labeled fluorescent fusion proteins in mouse ESCs for fluorescence loss during differentiation. We identified SET, which displayed a rapid isoform shift during early differentiation from the predominant isoform in ESCs, SETα, to the primary isoform in differentiated cells, SETβ, through alternative promoters. SETα is selectively bound and regulated by pluripotency factors. SET depletion causes proliferation slowdown and perturbed neuronal differentiation in vitro and developmental arrest in vivo, and photobleaching methods demonstrate SET's role in maintaining a dynamic chromatin state in ESCs. This work identifies an important regulator of pluripotency and early differentiation, which is controlled by alternative promoter usage.
胚胎干细胞（ESCs）受多能性相关转录因子与染色质调节因子的共同调控。为了鉴定其他的干细胞调控因子，我们在小鼠 ESCs 中筛选了一个内源性标记荧光融合蛋白文库，以在分化过程中检测荧光丢失。我们鉴定出 SET，它在早期分化过程中发生快速的异构体转换，从 ESCs 中的主要异构体 SETα转换为分化细胞中的主要异构体 SETβ，通过不同的启动子。SETα 被多能性因子选择性结合和调控。SET 耗竭导致细胞增殖减缓和体外神经分化紊乱，以及体内发育停滞，光漂白方法证明了 SET 在维持 ESCs 中动态染色质状态中的作用。这项工作鉴定出一个多能性和早期分化的重要调控因子，其受到不同启动子使用的控制。
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