小柯机器人

德国马克斯-普朗克免疫生物学和表观遗传学研究所Nicola Iovino、瑞士弗里德里希-米歇尔生物医学研究所Luca Giorgetti等研究人员合作发现，HP1驱动果蝇早期胚胎的从头3D基因组重新组织。相关论文于2021年4月14日在线发表在《自然》杂志上。

通过结合染色体构象捕获（Hi-C）、染色质免疫沉淀与高通量测序（ChIP–seq）、3D DNA荧光原位杂交（3D DNA FISH）和聚合物模拟，研究人员发现了异染色质蛋白1a（HP1a）在果蝇早期发育过程中对于从头3D基因组组织至关重要。HP1a在着丝粒异构体染色质上的结合是建立着丝粒周边区域聚集所必需的。此外，染色体臂内的HP1a结合负责整个染色体折叠，并在B区室的形成中起重要作用。

但是，HP1a的缺失不会影响A区室，这表明不同的分子机制会分隔活跃的染色体区域。这个工作确定了HP1a是一种表观遗传调控因子，参与建立早期胚胎基因组的整体结构。

据悉，3D基因组组织的基本特征是在早期胚胎中重新建立的，包括着丝粒周围区域的聚集、染色体臂的折叠以及染色体的分离，形成活跃的（A-）和不活跃的（B-）区室。然而，驱动从头组织的分子机制仍然未知。

附：英文原文

Title: HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Author: Fides Zenk, Yinxiu Zhan, Pavel Kos, Eva Lser, Nazerke Atinbayeva, Melanie Schchtle, Guido Tiana, Luca Giorgetti, Nicola Iovino

Issue&Volume: 2021-04-14

Abstract: Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering of pericentromeric regions, the folding of chromosome arms and the segregation of chromosomes into active (A-) and inactive (B-) compartments. However, the molecular mechanisms that drive de novo organization remain unknown1,2. Here, by combining chromosome conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), 3D DNA fluorescence in situ hybridization (3D DNA FISH) and polymer simulations, we show that heterochromatin protein 1a (HP1a) is essential for de novo 3D genome organization during Drosophila early development. The binding of HP1a at pericentromeric heterochromatin is required to establish clustering of pericentromeric regions. Moreover, HP1a binding within chromosome arms is responsible for overall chromosome folding and has an important role in the formation of B-compartment regions. However, depletion of HP1a does not affect the A-compartment, which suggests that a different molecular mechanism segregates active chromosome regions. Our work identifies HP1a as an epigenetic regulator that is involved in establishing the global structure of the genome in the early embryo.

DOI: 10.1038/s41586-021-03460-z

Source: https://www.nature.com/articles/s41586-021-03460-z

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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