2025-09-25 デューク大学
<関連情報>
- https://pratt.duke.edu/news/mapping-dark-genome/
- https://www.science.org/doi/10.1126/science.adl1988
機械感受性ゲノムエンハンサーはマトリックスの硬さに対する細胞応答を増強するMechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness
Brian D. Cosgrove, Lexi R. Bounds, Carson Key Taylor, Alan L. Su, […] , and Charles A. Gersbach
Science Published:25 Sep 2025
DOI:https://doi.org/10.1126/science.adl1988
Abstract
Epigenetic control of gene expression and cellular phenotype is influenced by changes in the local microenvironment, yet how mechanical cues 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 class of genomic enhancers that responds to the mechanical microenvironment. These “mechanoenhancers” can be preferentially activated on either soft or stiff extracellular matrix contexts and regulate transcription to influence critical cell functions including apoptosis, adhesion, proliferation, and migration. Epigenetic editing of mechanoenhancers reprograms the cellular response to the mechanical microenvironment and modulates the activation of disease-related genes in lung fibroblasts from healthy and fibrotic donors. Epigenetic editing of mechanoenhancers holds potential for precise targeting of mechanically-driven diseases.
