在基底分辨率上对基因调节元件的整合剖析
Zeyu Chen1,2,3, Nauman Javed1,2,3, Molly Moore2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Cell genomics
|June 30, 2023
概括
研究人员在基因增强剂中确定了关键的DNA基,该基因增强剂控制T细胞中的CD69表达. 基编辑揭示了这些序列是如何调节基因活动和细胞反应的.
科学领域:
- 基因组学就是基因组学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 基因调节元件众多,但它们的功能序列被人们理解得很少.
- 在它们的原生染色体环境中剖析调节元素是具有挑战性的.
研究的目的:
- 识别特定的序列动图和基因,对增强器功能至关重要.
- 了解T细胞中CD69诱导的调节机制.
主要方法:
- 表观遗传性扰动 表观遗传性扰动
- 编辑基础编辑
- 深度学习是一种深度学习.
- 对CD69免疫位点的分析.
主要成果:
- 在CD69增强剂中的~170个基区间被确定为关键.
- 特定的C-to-T基编辑减少了增强剂的可访问性,乙化和CD69表达.
- 关键的转录因子 (GATA3,TAL1,BHLHE40) 相互作用是相关的.
结论:
- 这项研究为剖析生物中的监管元素提供了一个框架.
- GATA3和BHLHE40之间的相互作用对于快速的T细胞反应至关重要.
- 识别的功能变异可以为未来的基因调节研究提供信息.
相关概念视频
Cis-regulatory Sequences
10.0K
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...
10.0K
Regulation of Expression at Multiple Steps
947
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
947
Regulation of Expression Occurs at Multiple Steps
3.1K
3.1K
Combinatorial Gene Control
8.4K
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...
8.4K
Structure of a Gene
12.6K
A gene is the fundamental unit of heredity. Every individual has two copies of each gene, one inherited from each parent. Although most people contain the same genes, there is a small fraction that is slightly different amongst people. A gene with a small difference in its sequence of DNA bases forms different alleles, contributing to different phenotypes.
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
However, only 1% of the DNA is composed of genes that encode proteins; the rest, 99% is non-coding DNA. This non-coding DNA performs...
12.6K
RNA Polymerase II Accessory Proteins
9.3K
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...
9.3K


