在T细胞激活后维持X染色体无活化需要NF-κB信号传递
Katherine S Forsyth1, Natalie E Toothacre1, Nikhil Jiwrajka1,2
1Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Science immunology
|October 4, 2024
概括
T细胞激活会触发不活跃的X染色体 (Xi) 上的表观遗传变化,涉及NF-κB信号传递. 这一过程对于维持X染色体失活 (XCI) 和调节女性的基因表达至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 遗传学 遗传学 是一个
背景情况:
- X染色体不活化 (XCI) 可以使两性之间的基因剂量相等.
- 在未刺激的T细胞中,不活跃的X染色体 (Xi) 缺乏特定的RNA和对XCI维持至关重要的修饰.
- 这些修改在T细胞刺激后恢复.
研究的目的:
- 调查T细胞中的Xi的等位基因特异性基因表达和表观基因组概况.
- 了解T细胞受体 (TCR) 信号在XCI维持中的作用.
主要方法:
- 分析T细胞中等位基因特异性基因表达和表观基因组概况.
- 调查TCR参与和NF-κB信号干扰对XistRNA局部化和X链接基因表达的影响.
主要成果:
- 未刺激的T细胞' Xi是用H3K27me3进行剂量补偿和丰富的,但不是H2AK119-ubiquitin (Ub).
- 刺激T细胞导致H2AK119-Ub在Xi上积累.
- NF-κB信号传递对于XistRNA局部化到Xi和适当的X链基因表达是必不可少的.
结论:
- T细胞激活会诱导Xi上的动态表观遗传修饰.
- NF-κB信号传递是T细胞中XCI维持的关键调节者.
- 这项研究揭示了女性T细胞中NF-κB通路和XCI之间的新联系.
相关概念视频
NF-κB-dependent Signaling Pathway
7.3K
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...
7.3K
X-Inactivation
38.2K
The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.
38.2K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K
T Cell Activation and Clonal Selection
680
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
680
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
T Cell Types and Functions
959
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
959


