Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.
Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation.
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DOI：
10.1016/j.stemcr.2017.08.021
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发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Meshorer E
中科院分区：
文献类型：
--
作者：
Edupuganti RR;Harikumar A;Aaronson Y;Biran A;Sailaja BS;Nissim-Rafinia M;Azad GK;Cohen MA;Park JE;Shivalila CS;Markoulaki S;Sze SK;Jaenisch R;Meshorer E
胚胎干细胞（ESCs）受多能性相关转录因子和染色质调节因子共同调控。为了鉴定额外的干细胞调节因子，我们筛选了小鼠ESC中内源性标记的荧光融合蛋白的文库，以确定分化过程中的荧光损失。我们鉴定了SET，其在早期分化期间通过替代启动子从ESC中的主要同种型SETα快速转变为分化细胞中的主要同种型SETβ。SETα被多能性因子选择性地结合和调节。SET耗竭导致体外增殖减缓和神经元分化紊乱以及体内发育停滞，并且光漂白方法证明了SET在维持ESC中动态染色质状态中的作用。这项工作确定了一个重要的调节多能性和早期分化，这是由替代启动子使用控制。我们发现SETα在ESC分化过程中被快速下调SETα在分化过程中被多能性因子调节并被SETβ取代SETα/SETβ转换对ESC分化至关重要SETα调节ESC中的染色质可塑性在这篇文章中，Meshorer和同事筛选了他们生成的内源性标记的荧光文库（参见Harikumar等人的随附论文）。并鉴定了一种连接体组蛋白伴侣SET/TAF-I，其参与调节小鼠ESC多能性和早期分化决定。他们表明，SET有两种亚型，由替代启动子和多能性因子调节，在早期分化过程中转换。SETα/SETβ置换对ESC分化具有重要意义。
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. We identify SETα to be rapidly downregulated during ESC differentiation SETα is regulated by pluripotency factors and replaced by SETβ during differentiation SETα/SETβ switch is crucial for ESC differentiation SETα regulates chromatin plasticity in ESCs In this article, Meshorer and colleagues screen the endogenously tagged fluorescent library they generated (see the accompanying paper by Harikumar et al.) and identify a linker histone chaperone, SET/TAF-I, to be involved in regulating mouse ESC pluripotency and early differentiation decisions. They show that SET has two isoforms regulated by alternative promoters and pluripotency factors, which are switched during early differentiation. SETα/SETβ replacement is important for ESC differentiation.
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小鼠和人类胚胎干细胞中基因家族调节剂的系统鉴定。
影响因子：
14.9
作者：
Aaronson Y;Livyatan I;Gokhman D;Meshorer E
通讯作者：
Meshorer E