转录因子DNA结合和调节目标的重叠程度较低
Lakshmi Mahendrawada1, Linda Warfield1, Rafal Donczew1,2
1Fred Hutchinson Cancer Center, Seattle, WA, USA.
Nature
|April 16, 2025
概括
大多数转录因子 (TF) 具有双重作用,而不是专门的激活器或抑制器功能. 这项研究揭示了复杂的TF相互作用和远程基因调节,挑战了现有的模型.
科学领域:
- 分子生物学
- 遗传学
- 系统生物学
背景情况:
- 转录因子 (TFs) 从特定的DNA位点调节基因表达和染色质结构.
- 了解多个TF如何合作控制单个基因仍然是一个挑战.
- 主流模型表明TFs主要与基因上游结合,以调节转录.
研究的目的:
- 系统地研究转录因子在基因调节中的作用和相互作用.
- 挑战传统的金融服务模式,探索新的监管机制.
- 提供单个细胞类型内TF功能的综合调查.
主要方法:
- 对近乎完整的酵母TF组的TF结合和基因表达数据的综合分析.
- 试验性消耗TF以确定监管目标.
- 计算分析以映射TF结合位点和基因表达变化.
主要成果:
- 确定大多数TF具有双重功能,而不是作为激活器或抑制器的专用作用.
- 观察到TF结合部位和它们调节的基因之间有限的重叠.
- 发现了许多远离可检测的TF绑定站点的监管目标,这表明了新的监管机制.
结论:
- 这项研究揭示了TF功能更复杂的图景,大多数TF具有双重作用.
- 基因调节涉及到直接结合的机制,包括长距离的相互作用.
- 这项工作为TFs对基因表达的组合控制提供了重要的见解.
更多相关视频
相关概念视频
Cooperative Binding of Transcription Regulators
6.3K
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...
6.3K
Co-activators and Co-repressors
7.2K
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...
7.2K
Transcription Factors
75.5K
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...
75.5K
Cis-regulatory Sequences
9.6K
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...
9.6K
RNA Polymerase II Accessory Proteins
9.1K
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...
9.1K
General Transcription Factors
5.1K
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...
5.1K


