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by Hannah Buckelew
Manuel Rosa-Garrido, Ph.D., an assistant professor in the UAB Department of Biomedical Engineering, recently published an article in the journal Nature Cardiovascular Research, titled, “Histone H1.0 Couples Cellular Mechanical Behaviors to Chromatin Structure.”

One manner in which cells alter their microenvironment in response to physical and chemical stressors is via fibrosis. Rosa-Garrido and team sought to investigate how communication between extracellular stress and chromatin structure may act to regulate cellular mechanical behaviors. They found that tuning of histone H1 levels and chromatin compaction is necessary for response to stress stimuli and that the linker histone H1.0 isoform has a significant role in this process.

“We essentially found an unexpected role of linker histones to orchestrate cellular mechanical behaviors,” says Rosa-Garrido.

To investigate the role of linker histone isoforms in response to cellular stress, the research team examined single-cell RNA sequencing data to determine the natural variation in the isoforms along cells. After examining this linker histone in various organs, the team found that regardless of tissue of origin, linker histone H1.0 is more highly expressed than other linker histone variants.

The team also found that depletion of histone H1.0 prevents cytokine-induced fibroblast contraction, proliferation and migration via inhibition of a transcriptome comprising extracellular matrix, cytoskeletal and contractile genes.

“Our findings support a central role for histone H1.0 as a molecular regulator of fibroblast stress response,” says Rosa-Garrido. “We found that depletion of histone H1.0 in vivo prevents fibrosis in cardiac muscle.”

These findings identify an unexpected role of linker histones to orchestrate cellular mechanical behaviors, directly coupling force generation, nuclear organization and gene transcription.