人类基因组中增强剂-基因调节相互作用的百科全书
Andreas R Gschwind1,2, Kristy S Mualim1,3, Alireza Karbalayghareh4
1Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
bioRxiv : the preprint server for biology
|November 28, 2023
概括
研究人员使用先进的模型和实验在许多细胞类型中创建了大量增强剂-基因相互作用的资源. 这有助于理解基因调节,并将遗传变异与疾病联系起来.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 识别转录增强剂及其向基因对于理解基因调节至关重要.
- 人类遗传变异显著影响疾病,通常通过非编码区域.
- 目前用于绘制增强剂-基因相互作用的现有方法存在局限性.
研究的目的:
- 创建和评估一个全面的资源增强剂-基因监管相互作用.
- 开发和验证用于增强剂基因调节的最先进的预测模型.
- 为增强器功能提供见解,并改进疾病变体解释.
主要方法:
- 综合预测模型,染色质状态,3D接触和大规模的遗传扰乱 (ENCODE联盟).
- 开发了一个使用CRISPR扰动,eQTL和GWAS变体的系统基准测试管道.
- 创建了一个新的预测模型,ENCODE-rE2G,使用代扰动和监督机器学习.
主要成果:
- 在352种细胞类型和组织中绘制了超过1300万个增强剂-基因调控相互作用.
- 在预测增强剂-基因链接方面,ENCODE-rE2G模型取得了最先进的性能.
- 确定了增强器网络的全球性质以及影响增强器-促进器通信的因素.
结论:
- 开发的资源和模型显著推进了基因调节和人类遗传学的研究.
- 增强将非编码变体与复杂疾病的向基因和细胞类型联系起来的能力.
- 对增强剂功能的新见解,包括促进剂类的作用和增强剂-增强剂协同作用.
相关概念视频
02:36RNA Polymerase II Accessory Proteins
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...
01:58Cell Specific Gene Expression
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
02:02Cis-regulatory Sequences
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...
02:33Combinatorial Gene Control
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...
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:02Cis-regulatory Sequences
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...