哺乳动物新皮层的保存和分离的基因调节程序
Nathan R Zemke1,2, Ethan J Armand1,3, Wenliang Wang4
1Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Nature
|December 13, 2023
概括
研究灵长类和小鼠大脑中的基因调节揭示了 cis 调节元素如何塑造物种特异性特征. 这项研究揭示了驱动新皮层进化的保存和分离的基因组特征.
科学领域:
- 神经科学
- 基因组学
- 进化生物学
背景情况:
- 特定物种的特征来自于 cis 调节元素的变化.
- 了解新皮层在分子层面上的演变至关重要.
研究的目的:
- 研究人类,,和老鼠的原发动机皮层中的基因调节程序.
- 探索新皮层进化的分子和细胞机制.
主要方法:
- 单细胞多组测定 (基因表达,染色体可访问性,DNA甲基组,染色体构造).
- 在四个物种中分析了超过20万个细胞.
- 机器学习用于预测 cis 调节元件.
主要成果:
- 转录因子表达的差异与特定物种的表观基因组相关.
- 在3D基因组中可以看到保存和分离的调节特征.
- 可转移的元素占人体特异性调节元素的80%左右.
- 从动物到灵长类动物的基因组调节语法是保留的.
- 在识别功能性 cis 调节元件时的表观遗传保护辅助.
结论:
- 表观遗传和序列数据的整合增强了与神经特征相关的遗传变异的解释.
- 这项研究提供了新皮层进化的分子基础及其对神经疾病的影响.
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