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

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

PROVIDER: PRJNA310699 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3138910_1.fastq.gz	Fastqsanger.gz
	SRR3138910_2.fastq.gz	Fastqsanger.gz
	SRR3138920_1.fastq.gz	Fastqsanger.gz
	SRR3138920_2.fastq.gz	Fastqsanger.gz
	SRR3138911_1.fastq.gz	Fastqsanger.gz

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

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.

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Project description:Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. Therefore, we used simulated microgravity achieved by growing cells on a 3d clinostat to investigate whether the LINC complex acts to mediate responses to the microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.

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