Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization.
Epigenetic repression of ribosomal RNA transcription by ROCK-dependent aberrant cytoskeletal organization.
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DOI：
10.1038/srep28685
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发表时间：
2016-06-28
影响因子：
4.6
通讯作者：
Chang ZF
中科院分区：
文献类型：
--
作者：
Wu TH;Kuo YY;Lee HH;Kuo JC;Ou MH;Chang ZF
已知核糖体RNA（rRNA）的合成受细胞能量和增殖状态的调节。在这项研究中，我们研究了rRNA基因转录响应细胞骨架应力。我们的数据显示，在HeLa细胞的各向同性，但不是细长的微图案的细胞形状的限制，导致了一个显着的减少依赖于ROCK的rRNA转录。显性活性形式的ROCK的表达也抑制rRNA转录。各向同性约束和ROCK过度激活导致不同类型的异常F-肌动蛋白组织，但它们对rRNA转录的抑制作用也同样被组蛋白脱乙酰酶（HDAC）的抑制或Nesprin的显性负性形式的过表达逆转，Nesprin屏蔽了从肌动蛋白丝传递到核内部的信号。我们进一步表明，HDAC 1与rDNA基因的活性部分的结合通过ROCK过度活化而增加，从而减少H3 K9/14乙酰化并抑制转录。我们的研究结果表明，表观遗传控制的活性rDNA基因，抑制rRNA转录响应细胞骨架应力。
It is known that ribosomal RNA (rRNA) synthesis is regulated by cellular energy and proliferation status. In this study, we investigated rRNA gene transcription in response to cytoskeletal stress. Our data revealed that the cell shape constrained by isotropic but not elongated micropatterns in HeLa cells led to a significant reduction in rRNA transcription dependent on ROCK. Expression of a dominant-active form of ROCK also repressed rRNA transcription. Isotropic constraint and ROCK over-activation led to different types of aberrant F-actin organization, but their suppression effects on rRNA transcription were similarly reversed by inhibition of histone deacetylase (HDAC) or overexpression of a dominant negative form of Nesprin, which shields the signal transmitted from actin filament to the nuclear interior. We further showed that the binding of HDAC1 to the active fraction of rDNA genes is increased by ROCK over-activation, thus reducing H3K9/14 acetylation and suppressing transcription. Our results demonstrate an epigenetic control of active rDNA genes that represses rRNA transcription in response to the cytoskeletal stress.