NHR-23 and SPE-44 regulate distinct sets of genes during Caenorhabditis elegans spermatogenesis.

NHR-23 and SPE-44 regulate distinct sets of genes during Caenorhabditis elegans spermatogenesis.
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DOI:
10.1093/g3journal/jkac256
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发表时间:
2022-11-04
期刊:
G3 (Bethesda, Md.)
影响因子:
--
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其他
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精子发生是形成成熟雄配子的过程,是传递遗传信息所必需的。虽然许多工作已经确定了精子命运是如何促进和维持的,但对精子形态发生程序是如何执行的知之甚少。我们以前确定了一个新的作用,核激素受体转录因子,NHR-23,在促进秀丽隐杆线虫精子发生。NHR-23沿着SPE-44(另一种促进精子发生的转录因子)的缺失导致累加表型。通过RNA-seq,我们确定NHR-23和SPE-44调节不同的基因组。NHR-23和SPE-44的缺失产生了另一组差异调节的基因。NHR-23调节的基因富含磷酸酶,这与精子细胞从基因组静止到翻译后调节的转变一致。在寄生线虫猪蛔虫中,MFP 1和MFP 2控制主要精子蛋白的聚合,主要精子蛋白是驱动精子活力并作为促进排卵的信号的分子。NHR-23和SPE-44调节几种MFP 2旁系同源物,并且来自雄性生殖系的NHR-23缺失导致MSD/MFP 1和NSPH-2/MFP 2的定位缺陷。尽管NHR-23和SPE-44不转录调节酪蛋白激酶基因spe-6(精子发育的关键调节因子),但NHR-23+SPE-44耗尽后SPE-6蛋白丢失。总之,这些实验提供了关于NHR-23如何促进精子发生的第一个机制性见解,并为理解NHR-23和SPE-44之间的合成遗传相互作用提供了切入点。
Spermatogenesis is the process through which mature male gametes are formed and is necessary for the transmission of genetic information. While much work has established how sperm fate is promoted and maintained, less is known about how the sperm morphogenesis program is executed. We previously identified a novel role for the nuclear hormone receptor transcription factor, NHR-23, in promoting Caenorhabditis elegans spermatogenesis. The depletion of NHR-23 along with SPE-44, another transcription factor that promotes spermatogenesis, caused additive phenotypes. Through RNA-seq, we determined that NHR-23 and SPE-44 regulate distinct sets of genes. The depletion of both NHR-23 and SPE-44 produced yet another set of differentially regulated genes. NHR-23-regulated genes are enriched in phosphatases, consistent with the switch from genome quiescence to post-translational regulation in spermatids. In the parasitic nematode Ascaris suum, MFP1 and MFP2 control the polymerization of Major Sperm Protein, the molecule that drives sperm motility and serves as a signal to promote ovulation. NHR-23 and SPE-44 regulate several MFP2 paralogs, and NHR-23 depletion from the male germline caused defective localization of MSD/MFP1 and NSPH-2/MFP2. Although NHR-23 and SPE-44 do not transcriptionally regulate the casein kinase gene spe-6, a key regulator of sperm development, SPE-6 protein is lost following NHR-23+SPE-44 depletion. Together, these experiments provide the first mechanistic insight into how NHR-23 promotes spermatogenesis and an entry point to understanding the synthetic genetic interaction between nhr-23 and spe-44.
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