五脊椎动物ChIP-seq揭示了转录因子结合的进化动态
Dominic Schmidt1, Michael D Wilson, Benoit Ballester
1Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Science (New York, N.Y.)
|April 10, 2010
概括
基因调控迅速发展,大多数转录因子结合点在物种之间存在差异. 尽管保留了DNA偏好,TF结合分歧是由动机序列变化驱动的,为调节演变提供了洞察力.
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:
- 转录因子 (TF) 是基因表达的关键调节者.
- 了解基因调节的进化是解读物种多样性的关键.
研究的目的:
- 研究脊椎动物肝脏中两个关键TFs的全基因组结合模式.
- 探索跨物种TF结合点的进化动态和保护.
主要方法:
- 使用高通量测序 (ChIP-seq) 的染色体免疫沉.
- 在五种脊椎动物物种中,对CCAAT/增强剂结合蛋白α和肝细胞核因子4α进行了全基因组TF占用映射.
- 分析的重点是保存与特定物种的结合事件及其与DNA序列约束的关系.
主要成果:
- 虽然TF DNA结合偏好得到保留,但大多数结合事件是物种特异性的.
- 在所有五种物种中都观察到罕见的对齐结合事件.
- 约束差异在很大程度上归因于TF约束动机的序列变化.
- 丢失的结合事件很少在附近恢复,只有一半在10 kilobases.
结论:
- 在转录调节方面存在显著的物种间变异.
- 监管演变的特点是动态的TF绑定模式.
- 动图的序列变化是物种之间的结合分歧的主要驱动因素.
相关概念视频
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02:13Cooperative Binding of Transcription Regulators
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02:13Cooperative Binding of Transcription Regulators
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01:30General Transcription Factors
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02:02Cis-regulatory Sequences
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