Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz.

ABSTRACT: Cells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function are not well understood. Here, we show using a model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs, resulting in subsequent weakening of the tendon. In vitro studies using paired ATAC/RNAseq demonstrate that the loss of cellular tension rapidly reduces chromatin accessibility in the vicinity of Yap/Taz genomic targets while also increasing expression of genes involved in matrix catabolism. C

SUBMITTER: Jones DL 

PROVIDER: S-EPMC10235980 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature