猕猴胎儿大脑的3D基因组揭示了灵长类动物皮质发生过程中的进化创新。

IF 5.7 1区 化学 Q2 CHEMISTRY, PHYSICAL
Xin Luo, Yuting Liu, Dachang Dang, Ting Hu, Yingping Hou, Xiaoyu Meng, Fengyun Zhang, Tingting Li, Can Wang, Min Li, Haixu Wu, Qiushuo Shen, Yan Hu, Xuerui Zeng, Xiechao He, Lanzhen Yan, Shihua Zhang, Cheng Li, Bing Su
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引用次数: 53

摘要

阐明人类大脑进化的调控机制对理解人类认知和精神障碍至关重要。我们生成了多组学图谱,并构建了恒河猴皮质发生过程中三维基因组结构的高分辨率图谱。通过比较人类、猕猴和小鼠大脑的三维基因组,我们发现了许多人类特异性的染色质结构变化,包括499个拓扑相关结构域(TADs)和1266个染色质环。人类特异性回路在增强子-增强子相互作用中显著富集,受调控的基因在亚板中显示出人类特异性表达的变化,亚板是发育中的大脑的一个过渡区,对神经回路的形成和可塑性至关重要。值得注意的是,许多人类特异性的序列变化位于人类特异性的TAD边界和环锚点,这可能在人类中产生新的转录因子结合位点和染色质结构。总的来说,这些数据突出了比较3D基因组分析在剖析大脑发育和进化的调节机制方面的价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis.

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque, and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions, and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may generate new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.

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来源期刊
Journal of Chemical Theory and Computation
Journal of Chemical Theory and Computation 化学-物理:原子、分子和化学物理
CiteScore
9.90
自引率
16.40%
发文量
568
审稿时长
1 months
期刊介绍: The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
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