Replication-independent DNA methylation dynamics during post-testicular sperm maturation

很明显，精子在附睾转运过程中被广泛重塑，成熟精子的蛋白质和RNA含量不断变化。此外，越来越多的研究表明，表观遗传信息在精子成熟过程中发生了修饰。在我博士学习的第一年，我发现在附睾精子成熟过程中胞嘧啶甲基化模式是惊人的动态。使用全基因组亚硫酸盐测序（WGBS），我确定了DNA甲基化在精子从睾丸穿过附睾的头、体和尾时的广泛变化。鉴于精子是一种高度甲基化和浓缩的细胞类型，附睾转运导致精子DNA甲基化重编程是令人惊讶和新颖的。我的目标是解决DNA甲基化变化如何在不同精子群体之间发生的问题。我的方法是概括体外成熟相关的胞嘧啶甲基化动力学，以了解这些变化发生的机制。解决这些变化对潜在的后代意味着什么，并确定机制

It has become apparent that sperm are extensively remodeled during epididymal transit, with ongoing changes to the protein and RNA content of maturing sperm. In addition, an increasing number of studies have shown that epigenetic information is modified during the process of sperm maturation. During the first year of my PhD studies, I have discovered that cytosine methylation patterns are surprisingly dynamic during sperm maturation in the epididymis. Using whole genome bisulfite sequencing (WGBS), I identified widespread changes in DNA methylation as sperm move from the testes through the caput, corpus, and cauda of the epididymis. Given that sperm are a highly methylated and condensed cell type, it is surprising and novel that epididymal transit results in any DNA methylation reprogramming of sperm. I aim to address the question of how DNA methylation changes occur between different sperm populations. My approach is to recapitulate maturation-associated cytosine methylation dynamics in vitro to understand the mechanism by which these changes are occurring. Resolving what these changes mean for potential offspring and determining the mechanisms and factors leading to changes in methylation will have significant implications for both assisted reproduction, and for understanding how a father's environment impacts his children's well being.