增强剂-促进剂相互作用的网络分析突出显示了转录调节变异的细胞类型特定机制
Justin Koesterich1,2,3, Jiayi Liu1,2,3, Sarah E Williams4,5,6,7
1Graduate Programs in Molecular Biosciences, Rutgers The State University of New Jersey, 604 Allison Rd., Piscataway, NJ 08854, USA.
International journal of molecular sciences
|September 28, 2024
概括
增强剂-促进剂相互作用 (EPI) 揭示了细胞类型特定的基因调控网络. 这些网络有助于识别与神经精神疾病相关的变异,有助于理解疾病机制和开发诊断.
科学领域:
- 基因组学就是基因组学.
- 神经科学是一个神经科学.
- 系统生物学 系统生物学
背景情况:
- 基因表达依赖于细胞类型特定转录的调节元素.
- 在这些监管区域内识别与疾病相关的变异是具有挑战性的.
研究的目的:
- 创建增强剂-促进剂相互作用 (EPI) 网络,以识别与疾病相关的变异.
- 通过神经元分化的调节区域研究细胞类型的特异性.
主要方法:
- 在六种神经元细胞类型中构建EPI网络.
- 在EPI网络的监管区域内对变量丰富的分析.
- 检查细胞类型特异性和分化阶段.
主要成果:
- EPI网络突出了特定于细胞类型的监管架构.
- 在特定的细胞类型和网络亚结构中发现的神经精神疾病变体的丰富.
- 对变体转录破坏机制的洞察.
结论:
- 在功能性分析中,EPI可以识别和优先考虑与疾病相关的变异.
- EPI提高了对细胞类型特异性基因调节和变异效应的理解.
- 结果支持在诊断和药物开发中的应用.
相关概念视频
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
The Eukaryotic Promoter Region
16.2K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
16.2K
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
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
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
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


