人类转录效应器的高通量发现和表征
Josh Tycko1, Nicole DelRosso2, Gaelen T Hess1
1Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Cell
|December 16, 2020
概括
这项研究引入了HT-recruit,一种用于识别具有转录效应功能的核蛋白的新方法. 它揭示了新的激活剂和抑制剂,
科学领域:
- 分子生物学
- 基因组学
- 蛋白质功能分析
背景情况:
- 数以千计的核蛋白存在,但它们的具体转录作用在很大程度上是未知的.
- 识别调节基因表达的蛋白质对于理解细胞过程至关重要.
研究的目的:
- 开发一种可扩展的方法来识别蛋白质内的转录效应域.
- 创建具有特征基因调节功能的人类蛋白质的综合资源.
主要方法:
- 开发了HT-recruit,一种结合蛋白质招募,记者基因测试和高通量测序的综合测试.
- 应用深度突变扫描来绘制蛋白质-蛋白质相互作用表面和功能部位.
- 标记了238个蛋白质以确定最小的功能域.
主要成果:
- 确定了成千上万个蛋白质域的转录激活和抑制活动.
- 发现抑制器功能与进化年龄 (KRAB域) 和霍克斯基因组织 (Homeodomain抑制器) 之间的相关性.
- 描述了新的激活子域,包括一个分离的KRAB,并确定了短的抑制子域 (小到10个氨基酸).
结论:
- HT-recruit是一个强大的,可扩展的策略,用于赋予蛋白质域功能.
- 这项研究提供了600种人类蛋白质的宝贵资源,这些蛋白质具有已知的转录效应器功能.
- 这项研究有助于我们更好地理解核蛋白对基因的调节.
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