小柯机器人

德国马克斯·普朗克生物物理化学研究所Patrick Cramer研究小组在研究中取得进展。他们解析了核小体结合的SOX2和SOX11结构，并阐明了先锋因子的功能。相关论文发表在2020年4月22日出版的《自然》杂志上。

他们报告的SOX2的DNA结合结构域及其与核小体紧密同源物SOX11的冷冻电镜结构。结构表明SOX因子可以结合超螺旋位置2上的DNA并使其局部扭曲。这些因子还促进末端核小体DNA从组蛋白八聚体上的解离，从而增加了DNA的可及性。SOX因子与核小体的结合还可能导致组蛋白H4的N末端尾巴（包括赖氨酸16残基）重新定位。他们推测高度有序核小体不能进行这种重新定位，后者涉及H4末端与邻近的核小体。他们的结果表明，先锋转录因子可以利用结合能来启动染色质的开放，从而促进核小体的重塑和随后的转录。

据了解，干细胞多能、细胞分化和细胞重编程需要先锋转录因子。先锋因子可以与核小体DNA结合，从而能够从具有封闭染色质的基因组区域表达基因。SOX2是一个突出的先锋因子，对胚胎干细胞的多能性和自我更新至关重要。

附：英文原文

Title: Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function

Author: Svetlana O. Dodonova, Fangjie Zhu, Christian Dienemann, Jussi Taipale, Patrick Cramer

Issue&Volume: 2020-04-22

Abstract: ‘Pioneer’ transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming1,2. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells3. Here we report cryo-electron microscopy structures of the DNA-binding domains of SOX2 and its close homologue SOX11 bound to nucleosomes. The structures show that SOX factors can bind and locally distort DNA at superhelical location 2. The factors also facilitate detachment of terminal nucleosomal DNA from the histone octamer, which increases DNA accessibility. SOX-factor binding to the nucleosome can also lead to a repositioning of the N-terminal tail of histone H4 that includes residue lysine 16. We speculate that this repositioning is incompatible with higher-order nucleosome stacking, which involves contacts of the H4 tail with a neighbouring nucleosome. Our results indicate that pioneer transcription factors can use binding energy to initiate chromatin opening, and thereby facilitate nucleosome remodelling and subsequent transcription.

DOI: 10.1038/s41586-020-2195-y

Source: https://www.nature.com/articles/s41586-020-2195-y

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