沙紫铃猪睾丸发育过程中的 DNA 甲基化调控。

Regulation of DNA methylation during the testicular development of Shaziling pigs.

机构信息

College of Animal Science and Technology, Hunan Provincial Key Laboratory for Genetic Improvement of Domestic Animal, Hunan Agricultural University, Hunan, Changsha 410128, China.

出版信息

Genomics. 2022 Sep;114(5):110450. doi: 10.1016/j.ygeno.2022.110450. Epub 2022 Aug 19.

DOI:10.1016/j.ygeno.2022.110450

PMID:35995261

Abstract

DNA methylation is one of the key epigenetic regulatory mechanisms in development and spermatogenesis. However, the dynamic regulatory mechanisms of genome-wide DNA methylation during testicular development remain largely unknown. Herein, we generated a single-base resolution DNA methylome and transcriptome atlas of precocious porcine testicular tissues across three developmental stages (1, 75, and 150 days old). The results showed that the dynamic methylation patterns were directly related to the expression of the DNMT3A gene. Conjoint analysis revealed a negative regulatory pattern between promoter methylation and the positive regulation of 3'-untranslated region (3'UTR) methylation. Mechanistically, the decrease in promoter methylation affected the upregulation of meiosis-related genes, such as HORMAD1, SPO11, and SYCE1. Demethylation in the 3'UTR induced the downregulation of the INHBA gene and knockdown of INHBA inhibited cell proliferation by reducing the synthesis of activin A. These findings contribute to exploring the regulatory mechanisms of DNA methylation in testicular development.

摘要

DNA 甲基化是发育和精子发生中关键的表观遗传调控机制之一。然而，睾丸发育过程中全基因组 DNA 甲基化的动态调控机制在很大程度上仍不清楚。在此，我们生成了早熟猪睾丸组织在三个发育阶段（1、75 和 150 天）的单碱基分辨率 DNA 甲基组和转录组图谱。结果表明，动态甲基化模式与 DNMT3A 基因的表达直接相关。联合分析显示启动子甲基化与 3'非翻译区（3'UTR）甲基化的正调控之间存在负调控模式。从机制上讲，启动子甲基化的减少会影响减数分裂相关基因，如 HORMAD1、SPO11 和 SYCE1 的上调。3'UTR 中的去甲基化诱导 INHBA 基因的下调，而 INHBA 的敲低通过减少激活素 A 的合成抑制细胞增殖。这些发现有助于探索睾丸发育中 DNA 甲基化的调控机制。