Heat shock factor 5 is conserved in vertebrates and essential forspermatogenesis in zebrafish

Abstract

Heat shock factors (Hsfs) are transcription factors that regulate response to heat shock and to variety of other environmental and physiological stimuli. Four HSFs (HSF1-4) known in vertebrates till date, perform a wide variety of functions from mediating heat shock response to development and gametogenesis. Here, we describe a new yet conserved member of HSF family, Hsf5, which likely exclusively functions for spermatogenesis. The hsf5 is predominantly expressed in developing testicular tissues, in comparison to wider expression reported for other HSFs. HSF5 loss causes male sterility due to drastically reduced sperm count, and severe abnormalities in remaining few spermatozoa. While hsf5 mutant female did not show any abnormality. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis. The hsf5 mutants indeed show misregulation of a substantial number of genes regulating cell cycle, DNA-damage repair, apoptosis and cytoskeleton proteins. We also show that Hsf5 physically binds to majority of these differentially expressed genes, suggesting its direct role in regulating the expression of many genes important for spermatogenesis.