不同的辅助因子依赖定义了不同类型的人类增强剂
Christoph Neumayr1,2, Vanja Haberle1, Leonid Serebreni1,2
1Research Institute of Molecular Pathology, Vienna BioCenter, Vienna, Austria.
Nature
|June 1, 2022
概括
研究人员根据辅助因子需求对人体增强剂进行了分类,揭示了绕过常见蛋白质的不同类型. 这一发现为了解基因调节和增强剂特异性提供了新的框架.
科学领域:
- 基因组学
- 分子生物学
- 表观遗传学
背景情况:
- 多细胞生物依赖于差异性基因转录,主要由基因组增强剂调节.
- 增强剂通过转录因子招募辅助因子,但并非所有辅助因子都是普遍要求的.
- 基于辅因子依赖的不同增强剂类型的存在以前是不清楚的.
研究的目的:
- 根据它们的辅助因子依赖来分类人类增强剂.
- 建立理解增强剂序列,染色质多样性和基因调节作用的框架.
- 在辅助因子耗尽时调查增强剂活性变化.
主要方法:
- 在HCT116细胞中使用STARR-seq量化全基因组增强剂活性.
- 在八个关键辅助因子的快速降解后评估增强剂功能.
- 分析了不同类型的增强剂的序列和染色质特性.
主要成果:
- 确定了具有特定辅因子要求,序列和色素特征的不同增强剂类型.
- 发现独立于核心调解子单元MED14或BRD4的增强剂,调节单独的转录程序.
- 对于P53响应增强剂来说,Mediator是不可用的,而对于CCAAT/ TATA盒子基因或热冲击基因来说,BRD4是不必要的.
结论:
- 辅因子依赖性对增强剂进行分类,揭示了可以绕过广泛使用的辅因子的不同类型.
- 替代转录激活机制分离基因表达程序,为增强器功能提供概念框架.
- 这种分类增强了对增强剂特异性和基因表达中的调节作用的理解.
相关概念视频
Co-activators and Co-repressors
2.5K
2.5K
Transcription Factors
77.8K
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...
77.8K
General Transcription Factors
5.6K
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...
5.6K
Combinatorial Gene Control
8.4K
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...
8.4K
RNA Polymerase II Accessory Proteins
9.6K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.6K
Master Transcription Regulators
7.1K
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...
7.1K


