英国细胞与发育生物学学系Xiaoqi Feng研究团队探明了广泛的N4胞嘧啶甲基化对地钱精子功能至关重要。相关论文于2025年4月9日发表在《细胞》杂志上。

本研究表明，多形地茅的精子发生涉及两波广泛的DNA甲基化重编程。首先，5-甲基胞嘧啶（5mC）从转座子扩展到整个基因组。值得注意的是，第二波在整个基因区域安装了4mC，覆盖了精子中超过50%的CG位点。4mC需要在精子发生晚期特异性表达的甲基转移酶（MpDN4MT1a）。MpDN4MT1a的缺失会改变精子转录组，导致精子游泳和生育缺陷，并损害受精后的发育。他们的研究结果揭示了4mC在真核生物中广泛存在，鉴定了一个真核甲基转移酶家族，并阐明了4mC在生殖发育中的生物学功能，从而扩大了功能性真核生物DNA修饰的范围。

据了解，N4 -甲基胞嘧啶（N4-methylcytosine, 4mC）是原核生物中一种重要的DNA修饰，但其在真核生物中的相关性和存在性一直是个谜。

附：英文原文

Title: Extensive N4 cytosine methylation is essential for Marchantia sperm function

Author: James Walker, Jingyi Zhang, Yalin Liu, Shujuan Xu, Yiming Yu, Martin Vickers, Weizhi Ouyang, Judit Tálas, Liam Dolan, Keiji Nakajima, Xiaoqi Feng

Issue&Volume: 2025-04-09

Abstract: N4-methylcytosine (4mC) is an important DNA modification in prokaryotes, but its relevance and even its presence in eukaryotes have been mysterious. Here we show that spermatogenesis in the liverwort Marchantia polymorpha involves two waves of extensive DNA methylation reprogramming. First, 5-methylcytosine (5mC) expands from transposons to the entire genome. Notably, the second wave installs 4mC throughout genic regions, covering over 50% of CG sites in sperm. 4mC requires a methyltransferase (MpDN4MT1a) that is specifically expressed during late spermiogenesis. Deletion of MpDN4MT1a alters the sperm transcriptome, causes sperm swimming and fertility defects, and impairs post-fertilization development. Our results reveal extensive 4mC in a eukaryote, identify a family of eukaryotic methyltransferases, and elucidate the biological functions of 4mC in reproductive development, thereby expanding the repertoire of functional eukaryotic DNA modifications.

DOI: 10.1016/j.cell.2025.03.014

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00287-9