鉴定影响人类细胞中基因基因修饰的基因变异
Graham McVicker1, Bryce van de Geijn, Jacob F Degner
1Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Science (New York, N.Y.)
|October 19, 2013
概括
研究人员确定了影响基因组修饰和基因调节的DNA变异. 这些遗传因素会影响染色体状态,转录因子结合和整个基因组的基因表达.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 基因组蛋白修饰是调节染色质结构和基因表达的关键表观遗传标记.
- 控制精确基因组定位的DNA序列元素的基因组修饰仍然在很大程度上是未知的.
- 了解这些调节元素是解读基因调节和染色质状态的关键.
研究的目的:
- 识别影响基因组修饰和RNA聚合酶II (Pol II) 占用基因组范围的DNA序列变异 (定量特征位置).
- 研究DNA变异,转录因子结合和局部染色质修饰之间的关系.
- 为了确定远程调节变异是否会影响相关促进体的染色质状态和基因表达.
主要方法:
- 全基因组关联研究 (GWAS) 在约鲁巴淋巴细胞类细胞系 (LCL) 上进行.
- 定量特征位点 (QTLs) 分析被用来绘制影响基因组修饰的变异,Pol II占用,脱氧核糖酶I (DNase I) 灵敏度和核细胞定位的变异.
- 进行了相关性分析,以将转录因子结合部位的多态性与本地基因子修饰差异联系起来.
主要成果:
- 数以百计的全基因组定量特征位点 (QTLs) 影响基因组修饰和Pol II占用在LCL中被确定.
- 许多已识别的变异同时影响了多种染色质特征,包括各种基因质标记,Pol II占用,DNase I敏感性和核细胞定位.
- 转录因子结合部位多态性通常与局部基因组修饰差异相关,特定的转录因子与诱导的基因组修饰有关.
- 发现远端调节区域的变异常常改变连接的促进体中的染色质和基因表达.
结论:
- DNA序列变异在确定基因组修饰和染色质状态的格局方面发挥着重要作用.
- 特定的转录因子和它们的结合位多态性是DNA序列导向基因素修饰的关键媒介.
- 遗传变异可以产生远程效应,影响远程调节元件及其向促进体的染色质和基因表达.
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