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在老鼠和人类之间保护监管信息的原则

Yong Cheng¹, Zhihai Ma¹, Bong-Hyun Kim²

¹Department of Genetics, Stanford University, Stanford, CA 94305, USA.

|November 21, 2014

概括

基因调节机制的进化过程中,在促进体上保留了TF结合,但在远端元素上具有可变的结合. 占用保留的地点通常是类的,并为监管变体进行了丰富.

科学领域:

进化生物学是进化的生物学.
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

了解基因调节的演变对于破译物种分歧至关重要.
转录因子 (TFs) 在基因调节中起着关键作用.

研究的目的:

调查基因调控特征的进化原理,因为人类和小鼠的血统分离.
为了比较不同细胞类型和物种的转录因子占用率和相关的表观遗传信号.

主要方法:

为34个正统TF生成全基因组转录因子占用概况.
分析了TF结合谱,表观遗传信号和人与老鼠红色素原体,淋巴细胞和胚胎干细胞系中的协同关联模式.
将TF占用序列的基因组分布,结合基因,染色质状态和DNA甲基化偏好进行比较.

主要成果:

基因组分布,结合基因,染色体状态和TF占用序列的DNA甲基化偏好在很大程度上得到保留.
结合保护在TF和基因组位置之间有所不同,促进体结合比远端元素结合更保守.
占用保存的TF占用序列通常是类的,并与多个TF共同关联.
调节区域中的单核酸变异被丰富在占用量保留的TF占用序列中.

结论:

基因调控特征显示,自从人类与老鼠分歧以来,既有保存的,又有分歧的进化模式.
与遥远的监管元素相比,促进者地区的TF绑定保护率更高.
类TF占用序列及其对调控变异的丰富突出了它们的进化意义.

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