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Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.

Publication ,  Journal Article
Cosgrove, BD; Bounds, LR; Taylor, CK; Su, AL; Rizzo, AJ; Barrera, A; Crawford, GE; Hoffman, BD; Gersbach, CA
Published in: bioRxiv
January 10, 2024

Epigenetic control of cellular transcription and phenotype is influenced by changes in the cellular microenvironment, yet how mechanical cues from these microenvironments precisely influence epigenetic state to regulate transcription remains largely unmapped. Here, we combine genome-wide epigenome profiling, epigenome editing, and phenotypic and single-cell RNA-seq CRISPR screening to identify a new class of genomic enhancers that responds to the mechanical microenvironment. These 'mechanoenhancers' could be active on either soft or stiff extracellular matrix contexts, and regulated transcription to influence critical cell functions including apoptosis, mechanotransduction, proliferation, and migration. Epigenetic editing of mechanoenhancers on rigid materials tuned gene expression to levels observed on softer materials, thereby reprogramming the cellular response to the mechanical microenvironment. These editing approaches may enable the precise alteration of mechanically-driven disease states.

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Published In

bioRxiv

DOI

Publication Date

January 10, 2024

Location

United States
 

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Cosgrove, B. D., Bounds, L. R., Taylor, C. K., Su, A. L., Rizzo, A. J., Barrera, A., … Gersbach, C. A. (2024). Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness. BioRxiv. https://doi.org/10.1101/2024.01.10.574997
Cosgrove, Brian D., Lexi R. Bounds, Carson Key Taylor, Alan L. Su, Anthony J. Rizzo, Alejandro Barrera, Gregory E. Crawford, Brenton D. Hoffman, and Charles A. Gersbach. “Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.BioRxiv, January 10, 2024. https://doi.org/10.1101/2024.01.10.574997.
Cosgrove BD, Bounds LR, Taylor CK, Su AL, Rizzo AJ, Barrera A, et al. Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness. bioRxiv. 2024 Jan 10;
Cosgrove, Brian D., et al. “Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.BioRxiv, Jan. 2024. Pubmed, doi:10.1101/2024.01.10.574997.
Cosgrove BD, Bounds LR, Taylor CK, Su AL, Rizzo AJ, Barrera A, Crawford GE, Hoffman BD, Gersbach CA. Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness. bioRxiv. 2024 Jan 10;

Published In

bioRxiv

DOI

Publication Date

January 10, 2024

Location

United States