Nejire/dCBP-mediated histone H3 acetylation during spermatogenesis is essential for male fertility in Drosophila melanogaster

Abstract

Spermatogenesis in many species including Drosophila melanogaster is accompanied by major reorganisation of chromatin in post-meiotic stages, involving a nearly genome-wide displacement of histones by protamines, Mst77F and Protamine-like 99C. A proposed prerequisite for the histone-to-protamine transition is massive histone H4 hyper-acetylation prior to the switch. Here, we investigated the pattern of histone H3 lysine acetylation and general lysine crotonylation in D. melanogaster spermiogenesis to elucidate a possible role of these marks in chromatin reorganisation. Lysine crotonylation was strongest prior to remodelling and the deposition of this mark depended on the acetylation status of the spermatid chromatin. In contrast to H4 acetylation, individual H3 acetylation marks displayed surprisingly distinct patterns during the histone-to-protamine transition. We observed that Nejire, a histone acetyl transferase, is expressed during the time of histone-to-protamine transition. Nejire knock down led to strongly reduced fertility, which correlated with misshaped spermatid nuclei and a lack of mature sperm. protA and prtl99C transcript levels were reduced after knocking down Nejire. ProtB-eGFP, Mst77F-eGFP and Prtl99C-eGFP were synthesized at the late canoe stage, while histones were often not detectable. However, in some cysts histones persist in parallel to protamines. Therefore, we hypothesize that complete histone removal requires multiple histone modifications besides H3K18ac and H3K27ac. In summary, H3K18 and H3K27 acetylation during Drosophila spermatogenesis is dependent on Nejire or a yet uncharacterized acetyl transferase. We show that Nejire is required for male fertility since Nejire contributes to efficient transcription of protA and prtl99C, but not Mst77F, in spermatocytes, and to maturation of sperm.

The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility

“…Additionally, histone acetylation during the canoe stage of spermatogenesis is required for histone eviction in Drosophila [61]. Indeed, reduced acetylation levels lead to abnormal histone retention and protamine deficiency, which causes embryonic inviability in flies [61] and in mammals [40,62,63]. Future research investigating what specific PTMs are altered at the Histone-Protamine transition stage will help elucidate the molecular pathway(s) leading to CI.…”

“…Thus, it is possible that inhibition of the histone ubiquitination process mediates abnormal histone retention. Additionally, histone acetylation during the canoe stage of spermatogenesis is required for histone eviction in Drosophila [61]. Indeed, reduced acetylation levels lead to abnormal histone retention and protamine deficiency, which causes embryonic inviability in flies [61] and in mammals [40,62,63].…”

A putative de novo evolved gene required for spermatid chromatin condensation in Drosophila melanogaster

“…Several other transition proteins have been characterized in D. melanogaster, including Tpl94D, thmg-1, thmg-2, and Mst84B [53,58,59]. Collectively, the transition proteins vary in the stage of nuclear condensation at which they first appear and the range of nuclear shapes over which they are found [79], but otherwise match Atlas in their biochemical properties, transient expression, and localization throughout the nucleus. Compared to these other transition proteins, Atlas is present over a fairly narrow range of nuclear condensation stages and reaches its peak expression just prior to the onset of individualization.…”

The Role of Exosomal Epigenetic Modifiers in Cell Communication and Fertility of Dairy Cows

“…Non-exosomal epigenetic modification (especially acetylation) in histone affects embryo implantation and spermatogenesis [126,127]. It has been demonstrated that the expression of sperm hyperacetylated histone 4 (H4) was reduced in low fertility bulls which results in loose chromatin structures [126].…”