当前位置: X-MOL 学术Exp. Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Genetics, epigenetics and back again: Lessons learned from neocentromeres.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-02-14 , DOI: 10.1016/j.yexcr.2020.111909
Marina Murillo-Pineda 1 , Lars E T Jansen 1
Affiliation  

The duplication and segregation of the genome during cell division is crucial to maintain cell identity, development of organisms and tissue maintenance. Centromeres are at the basis of accurate chromosome segregation as they define the site of assembly of the kinetochore, a large complex of proteins that attaches to spindle microtubules driving chromosome movement during cell division. Here we summarize nearly 40 years of research focussed on centromere specification and the role of local cis elements in creating a stable centromere. Initial discoveries in budding yeast in the 1980s opened up the field and revealed essential DNA sequence elements that define centromere position and function. Further work in humans discovered a centromeric DNA sequence-specific binding protein and centromeric α-satellite DNA was found to have the capacity to seed centromeres de novo. Despite the early indication of genetic elements as drivers of centromere specification, the discovery in the nineties of neocentromeres that form on unrelated DNA sequences, shifted the focus to epigenetic mechanisms. While specific sequence elements appeared non-essential, the histone H3 variant CENP-A was identified as a crucial component in centromere specification. Neocentromeres, occurring naturally or induced experimentally, have become an insightful tool to understand the mechanisms for centromere specification and will be the focus of this review. They have helped to define the strong epigenetic chromatin-based component underlying centromere inheritance but also provide new opportunities to understand the enigmatic, yet crucial role that DNA sequence elements play in centromere function and inheritance.

中文翻译:

遗传学,表观遗传学和再来一次:从新着丝粒学中吸取的教训。

细胞分裂过程中基因组的复制和分离对于维持细胞身份,生物发展和组织维持至关重要。着丝粒是精确的染色体分离的基础,因为它们定义了动粒的组装位点,这是一种大型蛋白质复合物,附着在纺锤体微管上,在细胞分裂过程中驱动染色体运动。在这里,我们总结了近40年的研究,着重于着丝粒规格和局部顺式元素在创建稳定着丝粒中的作用。1980年代在发芽酵母中的最初发现打开了这一领域,并揭示了定义着丝粒位置和功能的基本DNA序列元件。在人类中的进一步工作发现了着丝粒DNA序列特异性结合蛋白,着丝粒α卫星DNA被发现具有从头播种着丝粒的能力。尽管早期发现遗传因子是着丝粒规格的驱动力,但在不相关的DNA序列上形成的新着丝粒在90年代被发现,将焦点转移到了表观遗传机制上。虽然特定的序列元件似乎不是必需的,但组蛋白H3变体CENP-A被确定为着丝粒规格中的关键组成部分。天然或实验诱导的新着丝粒,已成为了解着丝粒规格的机制的有见地的工具,将成为本综述的重点。
更新日期:2020-02-20
down
wechat
bug