Key result
Loss of function of myosin chaperones in zebrafish skeletal muscle cells triggers a complex transcriptional response, including up-regulation of unc45b, mediated by Heat shock factor 1 (Hsf1).
Skeletal muscle cells respond to defective myosin chaperones with a complex gene program mediated by Hsf1 activation.
BACKGROUND: Mutations in myosin chaperones Unc45b and Hsp90aa1.1 as well as in the Unc45b-binding protein Smyd1b impair formation of myofibrils in skeletal muscle and lead to the accumulation of misfolded myosin. The concomitant transcriptional response involves up-regulation of the three genes encoding these proteins, as well as genes involved in muscle development. The transcriptional up-regulation of unc45b, hsp90aa1.1 and smyd1b is specific to zebrafish mutants with myosin folding defects, and is not triggered in other zebrafish myopathy models. RESULTS: By dissecting the promoter of unc45b, we identify a Heat shock factor 1 (Hsf1) binding element as a mediator of unc45b up-regulation in myofibers lacking myosin folding proteins. Loss-of-function of Hsf1 abolishes unc45b up-regulation in mutants with defects in myosin folding. CONCLUSIONS: Taken together, our data show that skeletal muscle cells respond to defective myosin chaperones with a complex gene program and suggest that this response is mediated by Hsf1 activation.
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Etard et al. (2015) studied Myosin folding defects. Loss of function of myosin chaperones vs. Wild-type siblings was evaluated on Transcriptional response (up-regulation of unc45b and other genes). Loss of function of myosin chaperones in zebrafish skeletal muscle cells triggers a complex transcriptional response, including up-regulation of unc45b, mediated by Heat shock factor 1 (Hsf1).
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