G6PD在血管壁中协调全基因组DNA甲基化和基因表达
Christina Signoretti1, Sachin A Gupte1
1Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
International journal of molecular sciences
|December 9, 2023
概括
葡萄糖-6-酸盐脱酶 (G6PD) 影响血管中的DNA甲基化. 该G6PD变体通过改变基因表达和DNA甲基化模式来减少大动脉的硬.
科学领域:
- 表观遗传学和血管生物学
- 基因表达的代谢调节
背景情况:
- 包括DNA甲基化在内的表观遗传修饰对于基因调节至关重要,但它们在血管组织中的控制尚未完全理解.
- DNA甲基转移酶 (DNMT) 和脱甲基酶 (TET) 调节DNA甲基化,特别是在疾病条件下.
- 葡萄糖-6-酸脱酶 (G6PD) 在调节健康血管组织中的表观遗传调节者的作用尚不清楚.
研究的目的:
- 为了研究一种假设,即葡萄糖-6-酸盐脱酶 (G6PD) 修改了DNA甲基转移酶 (DNMT) 和脱甲基酶 (TET) 的表达和活性.
- 探索地中海G6PD变异对大鼠DNA甲基化,基因表达和血管性的影响.
- 阐明G6PD在调节血管表观遗传景观和功能的非正规功能.
主要方法:
- 使用了使用CRISPR编辑的老鼠,它们携带了地中海G6PD变种 (G6PDS188F).
- 进行了全基因组双硫酸盐测序,用于DNA甲基化分析.
- 进行RNA测序,用于基因表达概况和心声回声,用于大动脉硬度评估.
主要成果:
- 与野生类型相比,观察到G6PDS188F变种大鼠的大动脉中DNMTs (Dnmt1,Dnmt3a) 和TETs (Tet2,Tet3) 的显著更高的表达.
- 鉴定了17618个差异甲基化位点,具有与炎症,血管收缩,光滑肌肉细胞分化和脂肪酸代谢相关的高甲基化和低甲基化明显模式.
- 证明依赖G6PD衍生的NADPH的氧化增强了TET活性并抑制了DNMT活性,从而减少了G6PDS188F大动脉硬度.
结论:
- 确立了野生型和变种G6PD在调节健康血管组织内的DNA甲基化和基因表达方面发挥的新型作用.
- G6PDS188F变异与改变的表观遗传特征相关,并有助于减少大动脉硬度.
- 突出了代谢途径 (G6PD) 和表观遗传机制在维持血管健康方面的潜在联系.
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
Genomic Imprinting and Inheritance
34.5K
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...
34.5K
Cell Specific Gene Expression
13.6K
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...
13.6K
Human Genetics
583
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
583
Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Genome-wide Association Studies-GWAS
13.5K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
13.5K


