人类发育中的长脑的染色质可访问性图谱
Eirene Markenscoff-Papadimitriou1, Sean Whalen2, Pawel Przytycki2
1Department of Psychiatry, Langley Porter Psychiatric Institute, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
Cell
|July 2, 2020
概括
科学家在发育中的人类大脑中绘制了开放的染色体图,以找到控制基因表达的调节元素. 这本地图揭示了关键增强剂及其在神经发育和自闭症等疾病中的作用.
科学领域:
- 基因组学
- 神经科学
- 发育生物学
背景情况:
- 基因表达特异性对于人类大脑的发展至关重要.
- 了解驱动这种特异性的监管因素是解读神经发育过程的关键.
研究的目的:
- 在人类发育中的大脑中创建一个开放的染色体图谱.
- 确定和描述作为发育大脑增强剂的预测调节元件 (pRE).
- 研究这些元素在区域,时间和层状基因表达特异性的作用.
主要方法:
- 从切割的人类脑区和前额叶皮层生成开放色素图谱.
- 在开放的染色体区域内确定预测调节元素 (pRE).
- 与基因表达数据相关的染色质可访问性.
- 使用CRISPR激活 (CRISPRa) 和小鼠转基因实验来验证增强剂的功能.
主要成果:
- 识别出具有时间,区域和层状差异的可访问性.
- 发现了pRE可访问性和基因表达变异之间的相关性.
- 在调节自闭症风险基因SLC6A1的pRE中发现了新的功能变异.
- 对FEZF2和BCL11A基因附近的pRE进行了验证.
结论:
- 产生的地图是理解神经发育基因调节的宝贵资源.
- 在发育中的大脑中,pRE在细胞类型和特定区域的基因表达中起着重要作用.
- 这项工作为神经发育障碍的遗传基础提供了洞察力.
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