A Caenorhabditis elegans protein with a PRDM9-like SET domain localizes to chromatin-associated foci and promotes spermatocyte gene expression, sperm production and fertility

摘要

To better understand the tissue-specific regulation of chromatin state in cell-fate determination and animal development, we defined the tissue-specific expression of all 36 C . elegans presumptive lysine methyltransferase (KMT) genes using single-molecule fluorescence in situ hybridization (smFISH). Most KMTs were expressed in only one or two tissues. The germline was the tissue with the broadest KMT expression. We found that the germline-expressed C . elegans protein SET-17, which has a SET domain similar to that of the PRDM9 and PRDM7 SET-domain proteins, promotes fertility by regulating gene expression in primary spermatocytes. SET-17 drives the transcription of spermatocyte-specific genes from four genomic clusters to promote spermatid development. SET-17 is concentrated in stable chromatin-associated nuclear foci at actively transcribed msp (major sperm protein) gene clusters, which we term msp locus bodies. Our results reveal the function of a PRDM9/7-family SET-domain protein in spermatocyte transcription. We propose that the spatial intranuclear organization of chromatin factors might be a conserved mechanism in tissue-specific control of transcription. Author summary During animal development, the generation of diverse cell types, such as nerve cells or muscle cells, requires differential gene expression. Lysine methyltransferases (KMTs) help determine which regions of the genome and hence which genes are expressed in each cell type. To enable the study of KMT function in development, Engert et al. defined the spatial expression patterns of all 36 presumptive KMT genes in the nematode Caenorhabditis elegans . While one-third of KMT genes were expressed broadly, the expression of most KMT genes was restricted to only certain cell types. The KMT gene set-17 was expressed in sperm-producing cells, where it proved to be necessary for normal fertility. The SET domain of the SET-17 protein is similar to the SET domain of the mammalian KMT PRMD9, which functions in fertility in mammals; SET-17 lacks the other domains of PRDM9. The authors showed that set-17 promotes fertility in sperm cell precursors by enabling the expression of clusters of genes that are required for the generation of sperm. Unexpectedly, the SET-17 protein localized to distinct spatial regions in the nuclei of sperm cell precursors. The authors propose that the spatial organization of KMTs and other factors that control gene expression is a broadly used mechanism in cell-type-specific gene regulation.