2025年1月8日，美国宾夕法尼亚大学Ben E. Black等研究人员合作在《自然》杂志发表论文。该研究表明，卫星DNA的结构决定雌性减数分裂中着丝粒周围的包装。

研究人员发现，依赖序列的DNA形状通过一种保守的DNA形状识别染色质结构蛋白——高迁移率族AT-钩蛋白1（HMGA1），决定了雌性减数分裂中着丝粒周围卫星DNA的包装。在两种密切相关的小鼠物种M. musculus和M. spretus中，着丝粒周围的异染色质在不同的卫星上形成，这些卫星在狭窄DNA小沟的密度和HMGA1的招募上有所不同。

HMGA1优先结合M. musculus卫星，而在M. musculus卵母细胞中去除HMGA1会导致着丝粒周围卫星的巨大拉伸、着丝粒组织的破坏以及双极纺锤体组装的延迟。在M. musculus × spretus杂交卵母细胞中，去除HMGA1对M. musculus的着丝粒影响尤为显著，且微管与其着丝粒的附着受到损害。

因此，DNA形状影响着丝粒周围卫星的包装和染色体分离机制。研究人员提出，尽管着丝粒和着丝粒周围的DNA快速演化，但当卫星DNA采用被保守结构蛋白（如HMGA1）识别的DNA形状时，这些基本过程不会受到破坏。通过包装这些卫星，结构蛋白成为着丝粒和着丝粒周围染色质的一部分，这暗示着一种演化策略，即通过降低大规模卫星扩展的代价来应对这一挑战。

据介绍，尽管着丝粒通过高度保守且至关重要的过程指导染色体的遗传，但着丝粒周围卫星DNA的丰度和序列仍在迅速演化。这种快速演化的影响尚不清楚。

附：英文原文

Title: Satellite DNA shapes dictate pericentromere packaging in female meiosis

Author: Dudka, Damian, Dawicki-McKenna, Jennine M., Sun, Xueqi, Beeravolu, Keagan, Akera, Takashi, Lampson, Michael A., Black, Ben E.

Issue&Volume: 2025-01-08

Abstract: The abundance and sequence of satellite DNA at and around centromeres is evolving rapidly despite the highly conserved and essential process through which the centromere directs chromosome inheritance1,2,3. The impact of such rapid evolution is unclear. Here we find that sequence-dependent DNA shape dictates packaging of pericentromeric satellites in female meiosis through a conserved DNA-shape-recognizing chromatin architectural protein, high mobility group AT-hook 1 (HMGA1)4,5. Pericentromeric heterochromatin in two closely related mouse species, M.musculus and M.spretus, forms on divergent satellites that differ by both density of narrow DNA minor grooves and HMGA1 recruitment. HMGA1 binds preferentially to M.musculus satellites, and depletion in M.musculus oocytes causes massive stretching of pericentromeric satellites, disruption of kinetochore organization and delays in bipolar spindle assembly. In M.musculus × spretus hybrid oocytes, HMGA1 depletion disproportionately impairs M.musculus pericentromeres and microtubule attachment to their kinetochores. Thus, DNA shape affects both pericentromere packaging and the segregation machinery. We propose that rapid evolution of centromere and pericentromere DNA does not disrupt these essential processes when the satellites adopt DNA shapes recognized by conserved architectural proteins (such as HMGA1). By packaging these satellites, architectural proteins become part of the centromeric and pericentromeric chromatin, suggesting an evolutionary strategy that lowers the cost of megabase-scale satellite expansion.

DOI: 10.1038/s41586-024-08374-0

Source: https://www.nature.com/articles/s41586-024-08374-0