对合成和基因组促进体中的组合性cis调节的分析
Jason Gertz1, Eric D Siggia, Barak A Cohen
1Center for Genome Sciences, Department of Genetics, Washington University in Saint Louis School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA.
Nature
|November 26, 2008
概括
科学家们开发了一种定量模型,用DNA序列来预测基因表达. 这种热力学模型准确地捕捉了转录因子结合部位如何协同工作,揭示了对基因调节的洞察力.
科学领域:
- 分子生物学分子生物学
- 系统生物学 系统生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录因子结合部位正在迅速被确定.
- 了解这些部位如何共同起作用来调节基因表达是至关重要的.
- 需要准确的定量模型来预测从促进体序列的基因表达.
研究的目的:
- 开发一种定量模型,从促进体序列中预测基因表达.
- 为了分析酵母 (Saccharomyces cerevisiae) 中的合成促进子库.
- 了解转录因子结合位点的组合作用.
主要方法:
- 在酵母中分析合成促进剂库.
- 基于转录因子平衡结合的热力学模型的开发.
- 将压制模型 (Mig1) 应用于S. cerevisiae基因组.
主要成果:
- 热力学模型准确地预测了表达变化的很大一部分.
- 该研究发现了诸如合作性和弱结合点的影响等现象.
- 在合成数据上训练的Mig1抑制模型预测了Mig1调节的基因在基因组中缺乏明显的结合点.
结论:
- 基于蛋白质-DNA和蛋白质-蛋白质相互作用的热力学模型对于预测基因表达是有效的.
- 复杂的生化反应似乎是这些初级相互作用的下游.
- 合成促进器库的定量分析是破译组合式 cis 调节的宝贵工具.
相关概念视频
Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Cis-regulatory Sequences
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
Cooperative Binding of Transcription Regulators
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...
Cooperative Binding of Transcription Regulators
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...
Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...


