在人类中转录因子结合的变化.
Maya Kasowski1, Fabian Grubert, Christopher Heffelfinger
1Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Science (New York, N.Y.)
|March 20, 2010
概括
转录因子 (TF) 结合的差异显著影响基因表达,有助于人类的个性化和物种分化. 这些变异,通常与遗传变化有关,为进化过程提供了洞察力.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 分子生物学分子生物学
背景情况:
- 基因表达变异对于物种化和表型多样性至关重要.
- 转录因子 (TF) 结合是影响基因表达的关键调节机制.
研究的目的:
- 研究跨个体和物种的转录因子结合的全基因组差异.
- 为了将TF结合变异与遗传变化和基因表达差异相关联.
主要方法:
- 使用染色体免疫沉和其后的测序 (ChIP-seq) 来绘制结合部位的地图.
- 在人类细胞系中分析了RNA聚合酶II (PolII) 和核因子kappaB (p65) 的结合位.
- 人类和黑猩猩的PolII结合模式进行了比较.
主要成果:
- 在人类个体之间观察到PolII和p65结合部位的显著差异 (分别为25%和7.5%).
- TF结合变异经常与单核酸多态和结构变异有关.
- TF结合的差异通常与改变的基因表达相关,表明功能相关性.
- 在人类和黑猩猩之间发现了PolII结合的广泛差异.
结论:
- 转录因子结合变异是个体和物种之间的差异的主要来源.
- 这些发现为表型多样性和物种化的遗传基础提供了洞察力.
相关概念视频
01:30General Transcription Factors
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...
02:16Transcription Factors
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...
02:16Transcription Factors
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...
02:13Cooperative 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...
02:13Cooperative 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...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...