NAC1 Regulates Somatic Cell Reprogramming by Controlling Zeb1 and E-cadherin Expression.
NAC1 Regulates Somatic Cell Reprogramming by Controlling Zeb1 and E-cadherin Expression.
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NAC1 通过控制 Zeb1 和 E-钙粘蛋白表达来调节体细胞重编程
DOI：
10.1016/j.stemcr.2017.07.002
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发表时间：
2017-09-12
影响因子：
5.9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Faiola F;Yin N;Fidalgo M;Huang X;Saunders A;Ding J;Guallar D;Dang B;Wang J
将体细胞重编程为诱导多能干细胞（iPSCs）是一个漫长且低效的过程。深入了解重编程背后的分子机制对于iPSCs的高效产生以及在医学中的安全应用至关重要。尽管人们已经付出了大量努力来识别重编程的促进因素和障碍，但这类因素的全部组成以及它们的作用机制还不清楚。在此，我们报道NAC1，一种与多能性相关的因子以及NANOG的伙伴，在重编程过程中多能性的建立是必需的。从机制上讲，NAC1通过一种双重调节机制对E - 钙黏蛋白的正确表达至关重要：它促进NANOG与E - 钙黏蛋白启动子结合并微调其表达；最重要的是，它通过转录抑制直接下调E - 钙黏蛋白抑制因子ZEB1，并通过miR - 200微小RNA的转录后激活间接下调ZEB1。因此，我们的研究揭示了多能性调节因子NAC1在促进体细胞高效重编程中一个此前未被重视的作用。
NAC1对高效产生iPSCs至关重要
NAC1促进NANOG与E - 钙黏蛋白启动子结合
NAC1与Zeb1启动子结合并抑制其表达
NAC1与miR - 200位点结合并间接激活E - 钙黏蛋白表达
深入理解体细胞重编程产生诱导多能干细胞（iPSCs）背后的分子机制对iPS技术的临床应用至关重要。在这方面，法奥拉等人揭示了转录因子NAC1如何协调E - 钙黏蛋白表达的转录和转录后控制以实现完整的重编程过程。
Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is a long and inefficient process. A thorough understanding of the molecular mechanisms underlying reprogramming is paramount for efficient generation and safe application of iPSCs in medicine. While intensive efforts have been devoted to identifying reprogramming facilitators and barriers, a full repertoire of such factors, as well as their mechanistic actions, is poorly defined. Here, we report that NAC1, a pluripotency-associated factor and NANOG partner, is required for establishment of pluripotency during reprogramming. Mechanistically, NAC1 is essential for proper expression of E-cadherin by a dual regulatory mechanism: it facilitates NANOG binding to the E-cadherin promoter and fine-tunes its expression; most importantly, it downregulates the E-cadherin repressor ZEB1 directly via transcriptional repression and indirectly via post-transcriptional activation of the miR-200 miRNAs. Our study thus uncovers a previously unappreciated role for the pluripotency regulator NAC1 in promoting efficient somatic cell reprogramming. NAC1 is critical for efficient iPSC generation NAC1 facilitates NANOG binding to E-cadherin promoter NAC1 binds to Zeb1 promoter and represses its expression NAC1 binds to the miR-200 loci and indirectly activates E-cadherin expression The in-depth comprehension of the molecular mechanisms underlying somatic cell reprogramming to generate induced pluripotent stem cells (iPSCs) is vital for the clinical applications of the iPS technologies. In that respect, Faiola et al. uncovered how the transcription factor NAC1 orchestrates the transcriptional and post-transcriptional controls of E-cadherin expression to achieve a complete reprogramming process.
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影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
14.8
作者：
Lee, Tong Ihn;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
间充质到上皮的转变启动并且是小鼠成纤维细胞核重编程所必需的
影响因子：
23.9
作者：
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通讯作者：
Pei, Duanqing
影响因子：
5.3
作者：
Mackler, SA;Korutla, L;Kalivas, PW
通讯作者：
Kalivas, PW
影响因子：
4
作者：
Pieters, Tim;van Roy, Frans
通讯作者：
van Roy, Frans