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核机械转导调控基因组组织和基因表达。

Regulation of genome organization and gene expression by nuclear mechanotransduction.

机构信息

Department of Electrical Engineering and Computer Science, Laboratory of Information and Decision Systems, Institute for Data, Systems and Society, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, USA.

Mechanobiology Institute, National University of Singapore, 119077 Singapore.

出版信息

Nat Rev Mol Cell Biol. 2017 Dec;18(12):717-727. doi: 10.1038/nrm.2017.101. Epub 2017 Oct 18.

Abstract

It is well established that cells sense chemical signals from their local microenvironment and transduce them to the nucleus to regulate gene expression programmes. Although a number of experiments have shown that mechanical cues can also modulate gene expression, the underlying mechanisms are far from clear. Nevertheless, we are now beginning to understand how mechanical cues are transduced to the nucleus and how they influence nuclear mechanics, genome organization and transcription. In particular, recent progress in super-resolution imaging, in genome-wide application of RNA sequencing, chromatin immunoprecipitation and chromosome conformation capture and in theoretical modelling of 3D genome organization enables the exploration of the relationship between cell mechanics, 3D chromatin configurations and transcription, thereby shedding new light on how mechanical forces regulate gene expression.

摘要

细胞能够感知其局部微环境中的化学信号,并将其转导至细胞核以调节基因表达程序,这一点已得到充分证实。尽管许多实验表明机械线索也可以调节基因表达,但潜在的机制还远不清楚。尽管如此,我们现在开始了解机械线索如何转导至细胞核,以及它们如何影响核力学、基因组组织和转录。特别是,超分辨率成像、全基因组 RNA 测序、染色质免疫沉淀和染色体构象捕获的应用以及 3D 基因组组织的理论建模方面的最新进展,使我们能够探索细胞力学、3D 染色质构象和转录之间的关系,从而为机械力如何调节基因表达提供新的认识。

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