自然遗传变异对增强剂选择和功能的影响
S Heinz1, C E Romanoski, C Benner
11] Department of Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, Mail Code 0651, La Jolla, California 92093, USA [2].
Nature
|October 15, 2013
概括
遗传变异影响基因调节和特征. 这项研究揭示了转录因子如何确定细胞身份和控制基因活性,有助于发现疾病变异.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 了解遗传变异如何影响核酸水平上的基因调节和表型仍然是一个挑战.
- 转录因子在控制基因表达方面发挥着关键作用,但它们对基因变异的反应的精确机制尚未完全阐明.
研究的目的:
- 研究自然遗传变异对转录因子结合,表观遗传学和基因表达的全基因组影响.
- 阐明确定血统和信号特异性转录因子在塑造细胞状态中的等级作用.
- 探索该模型在优先考虑与疾病相关的监管变异方面的实用性.
主要方法:
- 利用来自不同小鼠菌株的原发性巨细胞中的自然遗传变异作为体内突变发生屏幕.
- 评估了全基因组对转录因子结合 (确定血统和信号特异性),表观基因组状态和转录结果的影响.
- 分析数据以构建转录因子函数的层次模型.
主要成果:
- 证明确定血统的转录因子在建立表观遗传和转录基因状态中起着主要作用.
- 表明这些因素协作选择增强器区域,促进信号依赖因素的结合.
- 提供了大量的基因证据支持转录因子作用的等级模型.
结论:
- 转录因子函数的层次模型,其中血统因子先于信号依赖因子,由遗传变异数据支持.
- 限定的基因组数据集专注于确定血统的转录因子和关键的基因组修饰,可以有效地优先考虑与疾病相关的调节变异.
- 这种方法为了解遗传变异对基因调节和疾病的功能影响提供了一个强大的策略.
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