A Src-H3 acetylation signaling axis integrates macrophage mechanosensation with inflammatory response.

ABSTRACT: Macrophages are mechanosensitive cells that can exquisitely fine-tune their function in response to their microenvironment. While macrophage polarization results in concomitant changes in cell morphology and epigenetic reprogramming, how biophysically-induced signaling cascades contribute to gene regulatory programs that drive polarization remains unknown. We reveal a cytoskeleton-dependent Src-H3 acetylation (H3Ac) axis responsible for inflammation-associated histone hyperacetylation. Inflammatory stimuli caused increases in traction forces, Src activity and H3Ac marks in macrophages, accompanied by reduced cell elongation and motility. These effects were curtailed following disruption of H3Ac-signaling through either micropattern-induced cell elongation or inhibition of H3Ac readers (BRD

SUBMITTER: Veerasubramanian PK 

PROVIDER: S-EPMC8939266 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature