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Reactive oxygen species (ROS), which are a byproduct of oxidative metabolism, serve as signaling molecules in a number of physiological settings. However, if their levels are not tightly maintained, excess ROS lead to potentially cytotoxic oxidative stress. Accordingly, several transcriptional regulatory networks have evolved to include components that are highly ROS-responsive. Depending on the context, these regulatory networks can leverage ROS to respond to nutrient conditions, metabolism, or other physiological signals, or to respond to oxidative stress. However, ROS signaling is complex, so regulatory interactions between various ROS-responsive transcription factors are still being mapped out. Here we show that the transcription factor NRF2, a key regulator of the adaptive response to oxidative stress, directly regulates expression of HIF1A, which encodes HIF1α, a key transcriptional regulator of the adaptive response to hypoxia. We used an integrative genomics approach to identify HIF1A as a ROS-responsive transcript and we found an NRF2-bound antioxidant response element (ARE) approximately 30 kilobases upstream of HIF1A. This ARE sequence is deeply conserved, and we verified that it is directly bound and activated by NRF2. In addition, we found that HIF1A is upregulated in breast and bladder tumors with high NRF2 activity. Taken together, our results demonstrate that NRF2 targets a functional ARE at the HIF1A locus, and reveal a direct regulatory connection between two important oxygen responsive transcription factors.
Pubmed ID: 30241031 RIS Download
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Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsA web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
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