The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.
The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.
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DOI：
10.1038/srep38063
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发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Lele TP
中科院分区：
文献类型：
--
作者：
Alam SG;Zhang Q;Prasad N;Li Y;Chamala S;Kuchibhotla R;Kc B;Aggarwal V;Shrestha S;Jones AL;Levy SE;Roux KJ;Nickerson JA;Lele TP
细胞核与细胞外基质（ECM）的机械整合是通过细胞骨架和细胞核之间的连接建立的。假设这种整合可以介导 ECM 刚性的感知，但从其他机制解析核-细胞骨架连接的功能仍然是一个核心挑战。在这里，我们利用 LINC（核骨架和细胞骨架的连接器）复合物是细胞核与细胞骨架的已知分子连接器这一事实，并探究它如何调节全基因组转录对基质刚性的敏感性。我们发现，在 LINC 破坏后，基因机械敏感性得以保留，但方向发生了逆转。结合肌球蛋白抑制研究，我们确定了依赖核张力进行调节的基因。我们还表明，LINC 破坏不会减弱核形状对基质刚性的敏感性。我们的结果首次表明 LINC 复合物促进了整个基因组表达的机械调节。
Mechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity. We show that gene mechanosensitivity is preserved after LINC disruption, but reversed in direction. Combined with myosin inhibition studies, we identify genes that depend on nuclear tension for their regulation. We also show that LINC disruption does not attenuate nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex facilitates mechano-regulation of expression across the genome.
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影响因子：
4
作者：
Berk, Jason M.;Simon, Dan N.;Wilson, Katherine L.
通讯作者：
Wilson, Katherine L.
影响因子：
3.7
作者：
Montes de Oca R;Shoemaker CJ;Gucek M;Cole RN;Wilson KL
通讯作者：
Wilson KL
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Hodzic, D
影响因子：
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作者：
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通讯作者：
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