基于近距离的蛋白质相互作用和转录因子p65NF-κB/RELA的调节逻辑
Lisa Leib1, Jana Juli1, Liane Jurida1
1Rudolf Buchheim Institute of Pharmacology, Justus Liebig University, Giessen, Germany.
EMBO reports
|January 3, 2025
概括
研究人员绘制了活细胞中核因子kappa B (NF-κB) 的关键子单元p65/RELA的蛋白相互作用. 他们发现了超过350个相互作用伙伴,包括转录因子和表观遗传调节器,揭示了对基因调节的新见解.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录因子NF-κB的活性子单元p65/RELA的蛋白互动组在活细胞中仍然在很大程度上没有特征.
- 了解RELA的相互作用对于破译NF-κB通路调节及其在细胞过程中的作用至关重要.
研究的目的:
- 在不同的条件下,在活细胞中全面地绘制p65/RELA的蛋白互动组.
- 确定与RELA相互作用的新型转录因子和表观遗传调节剂.
- 阐明RELA及其合作伙伴控制的基因调节网络.
主要方法:
- 利用p65-miniTurbo融合蛋白和生物素标记用于体内蛋白质互动原子映射.
- 采用向RNAi屏幕来评估已识别的相互作用体的功能意义.
- 综合转录组和生物信息学分析以确定基因调控子网络.
主要成果:
- 在未经治疗的和IL-1α刺激的细胞中确定了350多个RELA相互作用体.
- 发现RELA相互作用主要依赖于二分化,而不是DNA结合.
- 发现了涉及RELA的特定基因调控子网络,这些子网络与ZBTB5,GLIS2,TFE3/TFEB和S100A8/A9.9等TF合作.
结论:
- 该研究为RELA提供了高分辨率的动态互动组图,为NF-κB研究提供了丰富的资源.
- 揭示了由RELA合作驱动的新型基因调节逻辑,解释了复杂的基因表达模式.
- 建立了一个新的框架,以了解RELA如何通过多种蛋白质相互作用协调基因表达.
相关概念视频
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
NF-κB-dependent Signaling Pathway
7.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.2K
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
Cooperative Binding of Transcription Regulators
6.3K
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...
6.3K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Transcription Factors
75.6K
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...
75.6K


