人类基因组中的DNA甲基化-环境相互作用
Rachel A Johnston1,2,3, Katherine A Aracena4, Luis B Barreiro4,5,6
1Department of Evolutionary Anthropology, Duke University, Durham, United States.
eLife
|February 26, 2024
概括
DNA甲基化模式影响基因调节和细胞对干扰素α等环境因素的反应. 然而,与早期生活逆境相关的地点并没有显示出增加的监管功能.
科学领域:
- 表观遗传学和基因组学
- 分子生物学分子生物学
- 系统生物学 系统生物学
背景情况:
- 大规模并行记者测试 (mSTARR-seq) 之前能够同时测试数百万个基因组位点的增强剂活性和DNA甲基化依赖增强剂活性.
- 基因甲基化是影响基因调节和细胞功能的关键表观遗传机制,对环境相互作用有潜在的影响.
研究的目的:
- 将mSTARR-seq应用于近乎全基因组的规模,询问数百万个CpG站点.
- 研究DNA甲基化的调节能力及其与细胞环境的相互作用,特别是对干扰素α (IFNA) 的反应.
- 评估与早期生命逆境相关的DNA甲基化模式是否预测功能调节作用.
主要方法:
- 应用mSTARR-seq查询几乎整个人类基因组,涵盖来自常见甲基化阵列和测序方法的CpG位点.
- 对响应IFNA刺激的DNA甲基化依赖调节活动的分析.
- mSTARR-seq的相关性确定了依赖甲基化的反应与人类巨细胞对流感病毒的转录反应.
主要成果:
- 含有CpG位点的基因组片段被丰富为调控能力.
- 甲基化依赖的调节活性对细胞环境敏感,IFNA反应被甲基标记显著减弱.
- 对IFNA的甲基化依赖反应预测了对流感病毒的甲基化依赖转录反应,支持DNA甲基化与环境的相互作用.
- 对于以前与早期生命逆境相关的地点,没有发现对功能调节影响的显著丰富.
结论:
- 预先存在的DNA甲基化模式可以调节对后续环境暴露的反应,与生物嵌入原则保持一致.
- 存在广泛的DNA甲基化环境相互作用,影响细胞对IFNA等刺激的反应.
- 基因甲基化对DNA的功能调节影响取决于情境,对于与早期生命逆境相关的网站而言,它并不普遍升高.
关键词:
国际货币基金组织 (IFNA) 的基金.在MPRA中,MPRA是MPRA.生物嵌入 生物嵌入染色体是一种染色体.早期的生活 逆境 逆境显基因组是一个表观基因组.基因表达的基因表达方式人类 人类 人类 人类 人类 人类 人类甲基化处理的方法更多相关视频
13:47Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution
Published on: February 24, 2015
25.5K
07:50Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
9.0K
相关概念视频
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Gene-Environment Interactions
318
Gene expression is a dynamic process that is significantly influenced by environmental factors. This interaction underlies the complex nature of biological development and the phenotypic differences observed among individuals, even among those with identical genetic makeups. Factors such as radiation, temperature, behavior, nutrition, and stress play pivotal roles in determining how genes are expressed. The concept of the reaction range is central to understanding this interaction. It posits...
318
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
Histone Modification
13.3K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
13.3K
Genomic Imprinting and Inheritance
34.4K
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
34.4K
Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K
