Department of Comparative Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
BMC Genomics. 2020 Aug 31;21(1):602. doi: 10.1186/s12864-020-07016-9.
The WD40-repeat containing proteins, including DDB1-CUL4-associated factors (DCAFs), are abundant and conserved proteins that play important roles in different cellular processes including spermatogenesis. DCAFs are subset of WD40 family proteins that contain WDxR motif and have been proposed to function as substrate receptor for Cullin4-RING-based E3 ubiquitin ligase complexes to recruit diverse proteins for ubiquitination, a vital process in spermatogenesis. Large number of WD40 genes has been identified in different species including mouse and human. However, a systematic expression profiling of WD40 genes in different tissues of mouse and human has not been investigated. We hypothesize that large number of WD40 genes may express highly or specifically in the testis, where their expression is uniquely regulated during testis development and spermatogenesis. Therefore, the objective of this study is to mine and characterize expression patterns of WD40 genes in different tissues of mouse and human with particular emphasis on DCAF genes expressions during mouse testicular development.
Publically available RNA sequencing (RNA seq) data mining identified 347 and 349 WD40 genes in mouse and human, respectively. Hierarchical clustering and heat map analyses of RNA seq datasets revealed differential expression patterns of WD40 genes with around 60-73% of the genes were highly or specifically expressed in testis. Similarly, around 74-83% of DCAF genes were predominantly or specifically expressed in testis. Moreover, WD40 genes showed distinct expression patterns during embryonic and postnatal testis development in mice. Finally, different germ cell populations of testis showed specific patterns of WD40 genes expression. Predicted gene ontology analyses revealed more than 80% of these proteins are implicated in cellular, metabolic, biological regulation and cell localization processes.
We have identified large number of WD40 family genes that are highly or specifically expressed in the testes of mouse and human. Moreover, WD40 genes have distinct expression patterns during embryonic and postnatal development of the testis in mice. Further, different germ cell populations within the testis showed specific patterns of WD40 genes expression. These results provide foundation for further research towards understanding the functional genomics and molecular mechanisms of mammalian testis development and spermatogenesis.
WD40 重复蛋白包含物，包括 DDB1-CUL4 相关因子 (DCAFs)，是丰富且保守的蛋白，在包括精子发生在内的不同细胞过程中发挥重要作用。DCAFs 是 WD40 家族蛋白的一个亚类，含有 WDxR 基序，据推测其作为 Cullin4-RING 基 E3 泛素连接酶复合物的底物受体发挥作用，以招募不同的蛋白质进行泛素化，这是精子发生过程中的一个重要过程。在不同物种中，包括小鼠和人类，已经鉴定出大量的 WD40 基因。然而，在小鼠和人类的不同组织中，WD40 基因的系统表达谱尚未被研究。我们假设大量的 WD40 基因可能在睾丸中高度或特异性表达，其表达在睾丸发育和精子发生过程中受到独特的调控。因此，本研究的目的是在小鼠睾丸发育过程中，对 WD40 基因在不同组织中的表达模式进行挖掘和特征描述，特别是 DCAF 基因的表达。
通过公开的 RNA 测序（RNA seq）数据挖掘，分别在小鼠和人类中鉴定出 347 个和 349 个 WD40 基因。RNA seq 数据集的层次聚类和热图分析显示 WD40 基因的表达模式存在差异，约 60-73%的基因在睾丸中高度或特异性表达。同样，约 74-83%的 DCAF 基因在睾丸中主要或特异性表达。此外，WD40 基因在小鼠胚胎和出生后睾丸发育过程中表现出不同的表达模式。最后，睾丸的不同生殖细胞群体表现出 WD40 基因表达的特定模式。预测的基因本体分析显示，这些蛋白质中有超过 80%参与细胞、代谢、生物调节和细胞定位过程。
我们已经鉴定出大量在小鼠和人类睾丸中高度或特异性表达的 WD40 家族基因。此外，WD40 基因在小鼠睾丸的胚胎和出生后发育过程中表现出不同的表达模式。此外，睾丸内不同的生殖细胞群体表现出 WD40 基因表达的特定模式。这些结果为进一步研究哺乳动物睾丸发育和精子发生的功能基因组学和分子机制提供了基础。
