三维超级增强器是与凝结物相关的 cis 调节性社区
Jie Lv1, Kelsey A Maher1, Li Dong1
1Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
Nucleic acids research
|March 9, 2026
概括
研究人员开发了BOUQUET,这是一个计算框架,用于识别核转录凝聚物中的cis-regulatory元素 (CREs) 和基因. 这种方法揭示了富含蛋白质并与细胞身份基因相关的"3D超级增强剂" (3D-SEs).
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 系统生物学 系统生物学
背景情况:
- 转录蛋白形成核凝聚物,含有诸如增强剂和促进剂之类的 cis调节元素 (CREs).
- 这些凝结物的确切功能和相关元素尚未完全理解.
- 识别与特定凝聚物相关的CREs对于理解基因调节至关重要.
研究的目的:
- 介绍一个新的计算框架,BOUQUET,用于将CREs和转录机械与核凝聚物中的目标基因联系起来.
- 确定与转录凝聚物相互作用的特别富含蛋白质的群体.
- 探索这些社区中蛋白质积累与基因表达之间的关系.
主要方法:
- 整合基因组拓,染色体占用数据和图形理论.
- 开发用于CRE基因和蛋白质机械分配的BOUQUET算法.
- 对蛋白质积累和基因表达表现型的分析.
- 显微镜验证预测的关联.
主要成果:
- 布奎特准确地将CREs和转录机制与目标基因联系起来.
- 识别了一组称为"三维超增强剂" (3D-SE) 的蛋白质丰富群体的子集.
- 3D-SE与细胞身份基因相关,并包含所有已知的基因,这些基因与胚胎干细胞中的联合激活剂凝聚物相互作用.
- 显微镜证实了基因在同一3D-SE和协同激活器点内共同定位和共同表达.
结论:
- 3D-SEs代表了协同激活核点,作为缩物相关的CREs和基因的枢纽.
- 布奎特框架提供了一种强大的方法来提名与凝结物相关的元素和基因.
- 这些发现突出了3D-SE在通过凝结物相互作用调节细胞身份基因中的作用.
相关概念视频
02:02Cis-regulatory Sequences
12.1K
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...
12.1K
02:02Cis-regulatory Sequences
4.3K
4.3K
02:13Cooperative Binding of Transcription Regulators
7.5K
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...
7.5K
02:13Cooperative Binding of Transcription Regulators
2.7K
2.7K
02:04Co-activators and Co-repressors
8.8K
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...
8.8K
02:04Co-activators and Co-repressors
3.2K
3.2K