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The mammalian LINC complex controls mechanosensing at a genome-wide level

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE77521 | GEO | 2017/01/20

SECONDARY ACCESSION(S): PRJNA310699

REPOSITORIES: GEO

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The mammalian LINC complex controls mechanosensing at a genome-wide level: miRNA-sequencing

Project description:Mechanical cues influence the shape, growth, and function of tissues and organs and are necessary for the development of engineered tissues. Yet, how cells sense mechanical cues and transduce them into changes in gene expression is not well understood. It is known that mechanical forces transmitted to the nucleus induce chromatin remodeling, promote DNA repair, contribute to the motion of intranuclear organelles and cause direct dissociation of protein complexes inside nuclei. Yet, the extent to which such signals impact gene expression is not understood. Because mechanical forces from the cytoskeleton to the nucleus interior are transmitted by the LINC (linker of nucleoskeleton-to-cytoskeleton) complex, we disrupted the LINC complex and performed genome wide expression studies using RNA sequencing. LINC disruption altered the expression of hundreds of genes at a genome-wide scale. We asked how LINC disruption affected the mechanosensitivity of individual genes by quantifying fold changes in gene expression on soft and stiff substrates. Remarkably, LINC disruption tended to preserve gene mechanosensitivity, but to reverse its direction. LINC disruption did not cause changes in nuclear shape, nor eliminated nuclear shape sensitivity to substrate rigidity. Our results show for the first time that the LINC complex regulates mechano-sensing at a genome-wide level, and argue for a distinct mechanism that does not require changes in nuclear morphology.

2017-01-20 | GSE77520 | GEO

The mammalian LINC complex controls mechanosensing at a genome-wide level: RNA-Seq

2017-01-20 | GSE77472 | GEO

The mammalian LINC complex controls mechanosensing at a genome-wide level

Project description:The mammalian LINC complex controls mechanosensing at a genome-wide level

| PRJNA310699 | ENA

The mammalian LINC complex regulates genome transcriptional responses to substrate rigidity.

Project description: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.

| S-EPMC5131312 | biostudies-literature

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