Snail1 transcription factor controls telomere transcription and integrity.
Snail1 transcription factor controls telomere transcription and integrity.
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DOI：
10.1093/nar/gkx958
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发表时间：
2018-01-09
影响因子：
14.9
通讯作者：
Canudas S
中科院分区：
文献类型：
--
作者：
Mazzolini R;Gonzàlez N;Garcia-Garijo A;Millanes-Romero A;Peiró S;Smith S;García de Herreros A;Canudas S
除了控制上皮向间充质转化(EMT)和细胞侵袭外，Snail1转录因子还为细胞提供了癌症干细胞的特征。由于端粒的维持对茎的形成至关重要，我们研究了Snail1对端粒完整性的控制。荧光原位杂交(FISH)分析表明，Snail1缺失的小鼠间充质干细胞(MSC)端粒改变显著增加，端粒变短。值得注意的是，Snail1缺失的MSC呈现出更高水平的端粒酶活性和被称为端粒重复序列包含RNA(Terra)的长非编码RNA，Terra是一种控制端粒完整性的RNA。因此，Snail1的表达下调了端粒酶基因(TERT)以及Terra 2q、11q和18q的表达。在转化生长因子β诱导的NMuMG细胞EMT过程中，TERA和TERT瞬时下调，与Snail1的表达相关。整体转录组分析表明，Terra的异位表达影响了EMT过程中诱导的一些基因的转录，如纤维连接蛋白，而TERT的异位表达不影响这些基因的转录。我们认为，Terra的Snail1抑制不仅是维持端粒所必需的，也是表达间充质基因子集所必需的。
Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion, the Snail1 transcriptional factor also provides cells with cancer stem cell features. Since telomere maintenance is essential for stemness, we have examined the control of telomere integrity by Snail1. Fluorescence in situ hybridization (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC) have both a dramatic increase of telomere alterations and shorter telomeres. Remarkably, Snail1-deficient MSC present higher levels of both telomerase activity and the long non-coding RNA called telomeric repeat-containing RNA (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q, 11q and 18q. TERRA and TERT are transiently downregulated during TGFβ-induced EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome analysis indicates that ectopic expression of TERRA affects the transcription of some genes induced during EMT, such as fibronectin, whereas that of TERT does not modify those genes. We propose that Snail1 repression of TERRA is required not only for telomere maintenance but also for the expression of a subset of mesenchymal genes.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
56.9
作者：
Azzalin, Claus M.;Reichenbach, Patrick;Lingner, Joachim
通讯作者：
Lingner, Joachim
影响因子：
50.3
作者：
Hsu, Dennis Shin-Shian;Wang, Hsiao-Jung;Yang, Muh-Hwa
通讯作者：
Yang, Muh-Hwa