Promoter hypermethylation of PIWI/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility
Promoter hypermethylation of PIWI/piRNA pathway genes associated with diminished pachytene piRNA production in bovine hybrid male sterility
复制标题
PIWI/piRNA 通路基因启动子高甲基化与牛杂种雄性不育中粗线期 piRNA 产量减少相关
DOI：
10.1080/15592294.2020.1738026
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发表时间：
2020-03-08
期刊：
影响因子：
3.7
通讯作者：
Zuo, Fuyuan
中科院分区：
文献类型：
--
作者：
Zhang, Gong-Wei;Wang, Ling;Zuo, Fuyuan
摘要杂种雄性不育是一种合子后生殖隔离机制，它导致物种形成。HMS的一个牛的例子是雅特（也称为dzo），一种牛磺酸牛（Bos taurus）和牦牛（Bos grunniens）的种间杂交。雅特HMS的分子机制还没有很好的理解。DNA甲基化和P元件诱导的睾丸萎缩（PIWI）相互作用RNA（piRNA）的表观遗传修饰是精子发生的重要调控因子。在这项研究中，我们研究了DNA甲基化模式和皮尔纳表达在成年睾丸的杂交不育雅特公牛和可育牛和牦牛公牛使用全基因组亚硫酸氢盐测序和小RNA-seq。雅特启动子甲基化与配子生成、皮尔纳代谢过程、精子发生和精子细胞发育中的DNA甲基化相关（P < 2.6 × 10−5）。雅特雄性不育与PIWI/皮尔纳通路基因（包括PIWIL 1、DDX 4、PLD 6、MAEL、FKBP 6、TDRD 1和TDRD 5）的启动子高甲基化相关沉默有关。沉默这些基因的下游效应是减少雅特睾丸中29至31个核苷酸的粗线期piRNA的产生。在转座因子基因座（LINEs，西内斯和LTRs）的高甲基化事件被发现在雅特。在雅特睾丸中，LINE来源的前粗线期piRNA增加，SINE来源的前粗线期piRNA减少。我们的数据表明，DNA甲基化影响PIWI/皮尔纳途径，并参与牛HMS精子发生过程中的基因表达和粗线期皮尔纳产生。DNA超甲基化和皮尔纳产生的破坏导致了可能驱动牛HMS的不成功的生殖细胞发育。
ABSTRACT Hybrid male sterility (HMS) is a postzygotic reproductive isolation mechanism that enforces speciation. A bovine example of HMS is the yattle (also called dzo), an interspecies hybrid of taurine cattle (Bos taurus) and yak (Bos grunniens). The molecular mechanisms underlying HMS of yattle are not well understood. Epigenetic modifications of DNA methylation and P-element induced wimpy testis (PIWI)-interacting RNA (piRNAs) are important regulators in spermatogenesis. In this study, we investigated DNA methylation patterns and piRNA expression in adult testes in hybrid infertile yattle bulls and fertile cattle and yak bulls using whole genome bisulphite-seq and small RNA-seq. Promoter hypermethylation in yattle were associated with DNA methylation involved in gamete generation, piRNA metabolic processes, spermatogenesis, and spermatid development (P < 2.6 × 10−5). Male infertility in yattle was associated with the promoter hypermethylation-associated silencing of PIWI/piRNA pathway genes including PIWIL1, DDX4, PLD6, MAEL, FKBP6, TDRD1 and TDRD5. The downstream effects of silencing these genes were diminished production of 29- to 31- nucleotide pachytene piRNAs in yattle testes. Hypermethylation events at transposable element loci (LINEs, SINEs, and LTRs) were found in yattle. LINE-derived prepachytene piRNAs increased and SINE-derived prepachytene piRNAs were reduced in yattle testes. Our data suggests that DNA methylation affects the PIWI/piRNA pathway and is involved in gene expression and pachytene piRNA production during spermatogenesis in bovine HMS. DNA hypermethylation and disruption of piRNA production contributed to unsuccessful germ cell development that may drive bovine HMS.