一个基因表达生物标志物的特征预测缺氧诱导因子-1调制
J Christopher Corton1, Brian Chorley1, Jie Liu1
1Center for Computational Toxicology and Exposure, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Chemico-biological interactions
|June 11, 2025
概括
一个新的基因表达生物标志物准确地识别了影响低氧诱导因子-1 (HIF-1) 的化学物质和遗传条件. 该工具有助于选影响HIF-1的环境因素,这对癌症和炎症性疾病至关重要.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 生物化学 生化学
背景情况:
- 低氧诱导因子-1 (HIF-1) 是一个关键的转录因子,调节细胞对低氧反应.
- HIF-1在癌症,炎症和缺血等疾病的病理生理学中发挥着重要作用.
- 识别HIF-1活性调节剂对于理解和治疗这些疾病至关重要.
研究的目的:
- 开发和验证一种基因表达生物标志物,以准确识别HIF-1的扰动.
- 评估生物标志物对HIF-1激活与HIF-2激活的特异性.
- 评估生物标志物在对影响HIF-1的环境化学品的高通量选中的实用性.
主要方法:
- 在低氧和HIF1A基因淘汰下,从人类细胞系的转录档案中识别了一种122基因的HIF-1生物标志物.
- 利用ChIP-Seq和Ingenuity路径分析来表征生物标志物基因并确定HIF-1作为顶级调节者.
- 通过使用参考化学品组和基因表达汇编的in-silico屏幕验证了生物标记物的准确性.
主要成果:
- 该122基因生物标记物被丰富为HIF-1结合基因和调节的代谢途径,如葡萄糖生成.
- 生物标志物准确地区分了HIF-1激活 (例如,通过HIF1A过度表达,VHL抑制) 和HIF-2活动.
- 在使用参考化学品集识别HIF-1激活时,获得了94.1%的平衡精度.
- 一个in-silico屏幕发现了许多潜在的激活剂,其中11个经过实验验证.
结论:
- 开发的HIF-1基因表达生物标志物是检测HIF-1通路干扰的特定和准确工具.
- 这种生物标志物可以有效地识别调节HIF-1活动的化学物质和遗传条件.
- 该工具具有显著的潜力,可以在各种生物环境中对影响HIF-1的环境相关化学品进行高通量选.
相关概念视频
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
01:30General Transcription Factors
5.2K
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...
5.2K
02:23Master 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
01:42What is Gene Expression?
167.1K
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
167.1K
01:58Cell Specific Gene Expression
13.5K
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...
13.5K
02:33Combinatorial Gene Control
8.3K
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...
8.3K