人类转录因子的DNA结合特异性
Arttu Jolma1, Jian Yan, Thomas Whitington
1Science for Life Center, Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, Sweden.
Cell
|January 22, 2013
概括
研究人员使用高通量SELEX和ChIP测序识别了由人类转录因子 (TF) 识别的DNA序列. 这项研究显著扩大了我们对TF-DNA结合特异性及其潜在机制的理解.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
背景情况:
- 转录因子 (TFs) 通过与特定的DNA序列结合来调节基因表达.
- 虽然已经确定了许多人体TF,但它们精确的DNA结合特异性往往是未知的.
- 了解TF-DNA相互作用对于破译基因调节至关重要.
研究的目的:
- 系统地分析人类转录因子的特定序列DNA结合.
- 为大多数人类TFs生成全面的具有约束力的配置文件.
- 阐明控制TF-DNA识别的新型决定因素和机制.
主要方法:
- 高通量SELEX (通过指数式丰富对联体的系统演化).
- ChIP测序 (染色体免疫沉测序) 是一种测序方法.
- 为TF绑定特异性开发计算模型.
主要成果:
- 生成了830个绑定配置文件,具有239个不同的TF绑定特征.
- 与之前的研究相比,已知的TF约束特征的覆盖率翻了一番.
- 确定了侧面序列元素 (A/T丰富的延伸),并揭示了同分体定向,间距和基堆叠在TF-DNA结合中的重要性.
结论:
- 开发了一种先进的结合模型,该模型包含了诸如侧面序列和基层堆叠相互作用等新的特性.
- 显著提高了对特定序列TF-DNA识别的理解.
- 为研究基因调节和TF功能提供了宝贵的资源.
相关概念视频
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...


