CTCF结合序列的特点有助于增强阻断活动
Felice H Tsang1,2, Rosa J Stolper2, Muhammad Hanifi2
1Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK.
Nucleic acids research
|August 6, 2024
概括
结合CCCTC-结合因子 (CTCF) 的绝缘体元素的理解很少. 这项研究开发了一个测试单个CTCF元素的系统,发现它们的增强剂阻断活性与保护或核心动机无关.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 增强剂和促进剂是经过充分研究的基因调节元件.
- 绝缘体元素,特别是那些结合CCCTC-结合因子 (CTCF) 的绝缘体元素的特征较少.
- 基因组背景显著影响CTCF站点的功能和活动.
研究的目的:
- 通过实验确定最小的单个CTCF元素的增强剂阻断活性.
- 评估CTCF元素在分化过程中对基因表达的影响.
- 通过在相同的位置测试元素来最大限度地减少基因组背景的影响.
主要方法:
- 开发了一个新的实验系统来测试单个CTCF元素.
- 测试了CTCF元素隔离增强剂与促进剂的能力.
- 通过标准化元素位置来最大限度地减少基因组上下文影响.
主要成果:
- 在CTCF元素增强剂阻断活性和进化保护之间没有发现相关性.
- 与共识核心序列的相似性或CTCF核心动机的数量没有预测阻断能力.
- 最强的阻断器包括CTCF核心动机上游的先前描述的元素.
- 在核心图案附近的非特征化的DNaseI足迹可能会影响功能.
结论:
- CTCF元素的功能不仅仅是由保存或核心动机决定的.
- 特定的序列,包括核心基因和附近DNaseI足迹的上游序列,对于增强器阻断至关重要.
- 开发了一种新的测定方法,用于统一和公正地分类CTCF元素.
相关概念视频
Cis-regulatory Sequences
9.8K
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...
9.8K
Eukaryotic Transcription Inhibitors
9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K
Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
Co-activators and Co-repressors
7.3K
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...
7.3K
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
Transcription Factors
75.7K
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...
75.7K


