GSE185603
Chromatin alterations during the epididymal maturation of mouse sperm refine the paternally inherited epigenome
Established dogma holds that all facets of chromatin organization and histone posttranslational modification are complete before sperm exits the testes. Using proteomic analysis to contrast immature spermatozoa and mature sperm from the epididymis, we find progressive changes in multiple histone posttranslational modifications, including H3K4me1, H3K27ac H3K79me2, H3K64ac, H3K122ac, H4K16ac, H3K9me2, and H4K20me3. In contrast, levels of H3K4me3 and H3K27me3 remained constant. Using chromatin immunoprecipitation coupled with deep sequencing, we find that changes in H3K27ac and H3K9me2 involve sharpening broad diffuse regions into narrow peaks, centered on promoters and distal enhancers driving embryonic development (H3K27ac) or tissue-specific genes sequestered in lamina-associated domains (H3K9me2). Maturing sperm contain the histone deacetylase enzymes HDAC1 and HDAC3, suggesting the NuRD complex may drive these changes. These data extend our understanding of germline programming and reveal that, in addition to trafficking noncoding RNAs, alterations to histone structure are a core feature of epididymal maturation. Overall design: Examination of 2 different histone modifications in post-testicular murine spermatozoa during epididymal maturation