近日，新加坡南洋理工大学Lars Nordenskiöld、Daniela Rhodes等研究人员合作揭示人类端粒染色质的圆柱状结构。相关论文于2022年9月14日在线发表在《自然》杂志上。

研究人员使用负染电子显微镜和单分子磁镊子来描述了3000bp长的端粒染色质纤维的特征。研究人员还获得了凝结的端粒四核小体及其二核小体单元的冷冻电镜结构。该结构显示了具有圆柱状排列核小体的紧密堆叠，以及异常短的核糖体重复长度，包括约132bp的DNA缠绕在组蛋白八聚体周围的连续超螺旋。这种圆柱状结构主要由H2A羧基端和组蛋白氨基端尾部以协同的方式稳定。圆柱状结构导致DNA螺旋的暴露，这可能使其容易受到DNA损伤和DNA损伤反应的影响。该构象也存在于另一种开放状态，其中一个核小体被解开并翻转出来，这暴露了组蛋白表面的酸性补丁。这项工作所揭示的结构特征阐明了参与端粒维护的蛋白因子能够以其紧凑的形式进入端粒染色质的机制。

据悉，端粒是真核生物染色体的末端，在衰老和癌症中起着关键的作用，并且是DNA损伤和DNA损伤反应的靶标。在分子水平上对端粒染色质的结构知之甚少。

附：英文原文

Title: Columnar structure of human telomeric chromatin

Author: Soman, Aghil, Wong, Sook Yi, Korolev, Nikolay, Surya, Wahyu, Lattmann, Simon, Vogirala, Vinod K., Chen, Qinming, Berezhnoy, Nikolay V., van Noort, John, Rhodes, Daniela, Nordenskild, Lars

Issue&Volume: 2022-09-14

Abstract: Telomeres, the ends of eukaryotic chromosomes, play pivotal parts in ageing and cancer and are targets of DNA damage and the DNA damage response1,2,3,4,5. Little is known about the structure of telomeric chromatin at the molecular level. Here we used negative stain electron microscopy and single-molecule magnetic tweezers to characterize 3-kbp-long telomeric chromatin fibres. We also obtained the cryogenic electron microscopy structure of the condensed telomeric tetranucleosome and its dinucleosome unit. The structure displayed close stacking of nucleosomes with a columnar arrangement, and an unusually short nucleosome repeat  length that comprised about 132bp DNA wound in a continuous superhelix around histone octamers. This columnar structure is primarily stabilized by the H2A carboxy-terminal and histone amino-terminal tails in a synergistic manner. The columnar conformation results in exposure of the DNA helix, which may make it susceptible to both DNA damage and the DNA damage response. The conformation also exists in an alternative open state, in which one nucleosome is unstacked and flipped out, which exposes the acidic patch of the histone surface. The structural features revealed in this work suggest mechanisms by which protein factors involved in telomere maintenance can access telomeric chromatin in its compact form.

DOI: 10.1038/s41586-022-05236-5

Source: https://www.nature.com/articles/s41586-022-05236-5