DNA甲基化影响着人类着丝粒的定位和功能，这一成果由Daniele Sorbonne UniversitFachinetti小组经过不懈努力而取得。该研究于2025年9月4日发表于国际一流学术期刊《自然—遗传学》杂志上。

为了解决这个问题，小组开发了一些工具来干扰着丝性DNAme，揭示它会影响CENP-A的定位。该课题组人员发现甲基化的快速缺失导致着丝粒蛋白结合增加和着丝粒结构改变，导致非整倍体和细胞活力降低。研究人员还证明了逐渐的着丝粒DNA去甲基化促进了细胞适应过程。总之，该课题组人员发现DNAme直接影响着CENP-A定位和着丝粒功能，为着丝粒DNAme的病理改变提供了机制见解。

研究人员表示，维持着丝粒的表观遗传特性对于防止基因组不稳定至关重要。着丝粒在表观遗传学上由组蛋白H3变体CENP-A定义。先前对人类着丝粒的研究表明，CENP-A与位于大量高甲基化重复序列中的低甲基化DNA区域有关，但这些DNA甲基化（DNAme）模式的功能重要性仍然知之甚少。

附：英文原文

Title: DNA methylation influences human centromere positioning and function

Author: Salinas-Luypaert, Catalina, Dubocanin, Danilo, Lee, Rosa Jooyoung, Andrade Ruiz, Lorena, Gamba, Riccardo, Grison, Marine, Velikovsky, Leonid, Angrisani, Annapaola, Scelfo, Andrea, Xu, Yuan, Dumont, Marie, Barra, Viviana, Wilhelm, Therese, Velasco, Guillaume, Losito, Marialucrezia, Wardenaar, Ren, Francastel, Claire, Foijer, Floris, Kops, Geert J. P. L., Miga, Karen H., Altemose, Nicolas, Fachinetti, Daniele

Issue&Volume: 2025-09-04

Abstract: Maintaining the epigenetic identity of centromeres is essential to prevent genome instability. Centromeres are epigenetically defined by the histone H3 variant CENP-A. Prior work in human centromeres has shown that CENP-A is associated with regions of hypomethylated DNA located within large arrays of hypermethylated repeats, but the functional importance of these DNA methylation (DNAme) patterns remains poorly understood. To address this, we developed tools to perturb centromeric DNAme, revealing that it causally influences CENP-A positioning. We show that rapid loss of methylation results in increased binding of centromeric proteins and alterations in centromere architecture, leading to aneuploidy and reduced cell viability. We also demonstrate that gradual centromeric DNA demethylation prompts a process of cellular adaptation. Altogether, we find that DNAme causally influences CENP-A localization and centromere function, offering mechanistic insights into pathological alterations of centromeric DNAme.

DOI: 10.1038/s41588-025-02324-w

Source: https://www.nature.com/articles/s41588-025-02324-w