The Function Of Sox30 During Mouse Spermiogenesis

The developmental progression of round spermatids into mature spermatozoa,termed spermiogenesis,requires multiple molecular events including profound nuclear restructuring and condensation,cytoplasmic removal,formation of an acrosome and assembly of the flagellum.Accordingly,a large number of proteins required for these events have to be synthesized at the onset of and throughout spermiogenesis.Due to a relatively inaccessible chromatin state during the late steps of spermiogenesis,pachytene spermatocytes and round spermatids are transcriptionally active,and specific mRNAs produced during these stages are stored and stabilized in cytoplasmic ribonucleoprotein(RNP)particles until their translation is required in later stage spermatids.The intricate mechanisms for precise activation of the haploid-stage expression program involve transcriptional and post-transcriptional regulation.Transcriptional reulation is the primary determinant of gene expression.Gene transcription is regulated by the binding of transcription factors to promoter motifs in the DNA sequence upstream of the protein coding region,thereby inducing changes in chromatin structure and modulating activity of the transcriptional machinery.Several transcription factors in mouse have been identified that are highly expression in post-meiotic germ cells.Defects in these transcription factors often induce a complete arrest in spermiogenesis and specific effects on male fertility.However,the molecular mechanisms controlling post-meiotic gene expression programs remain poorly understood.While many of these factors are conserved in human spermatogenesis,the study of mouse models is likely to provide insights into understanding the molecular mechanisms of human infertility.The Sox family members contain a DNA-binding HMG box and are key regulators of progenitor cell fate.Here,we report that expression of Sox30 is restricted to meiotic spermatocytes and postmeiotic haploids.Sox30 mutant males are sterile due to spermiogenic arrest at early round spermatid stage.Although most Sox30 mutant spermatocytes progress through meiosis,accumulation of diplotene spermatocytes indicates a delayed or impaired transition from meiotic to postmeiotic stages.Transcriptome analysis of isolated stage-specific spermatogenic cells reveals that Sox30 controls a core postmeiotic gene expression program that initiates as early as in late meiotic cells.Chromatin immunoprecipitation followed by deep-sequencing(Ch IP)confirmed specific enrichment of SOX30 to promoters of a subset of post-meiotic genes including Tnp1,Hils1,Ccdc54 and Tsks.These results define Sox30 as a crucial transcription factor that controls the transition from a late meiotic to a postmeiotic gene expression program and subsequent round spermatid development.