Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complex I is the most complicated of the multimeric enzymes that constitute the mitochondrial respiratory chain. It is encoded by both mitochondrial and nuclear genomes. We have previously characterized the human NDUFS8 gene that encodes the TYKY subunit. This essential subunit is thought to participate in the electron transfer and proton pumping activities of complex I. Here, we have analyzed the transcriptional regulation of the NDUFS8 gene. Using primer extension assays, we have identified two transcription start sites. The basal promoter was mapped to a 247 bp sequence upstream from the main transcription start site by reporter gene analysis in HeLa cells and in differentiated or non-differentiated C2C12 cells. Three Sp1 sites and one YY1 site were identified in this minimal promoter. Through gel shift analysis, all sites were shown to bind to their cognate transcription factors. Site-directed mutagenesis revealed that the YY1 site and two upstream adjacent Sp1 sites drive most of the promoter activity. This work represents the first promoter analysis for a complex I gene. Together with previous studies, our results indicate that YY1 and Sp1 control the expression of genes encoding proteins that are involved in almost all steps of the oxidative phosphorylation metabolism.
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PMID:YY1 and Sp1 activate transcription of the human NDUFS8 gene encoding the mitochondrial complex I TYKY subunit. 1195 26

Polycomb-group (PcG) proteins are chromatin-associated proteins that heritably repress gene activity in many organisms, including man. Two distinct human PcG complexes have been identified. The HPC/HPH PcG complex I contains the HPC, HPH, RING1, and BMI1 proteins, the EED/EZH2 PcG complex II contains the EED, EZH2, and YY1 proteins. Previously we found that the relative expression levels of proteins of the human PcG complexes I and II are severely deregulated in human tumors. These findings signify an important role for antibodies against human PcG proteins as diagnostic tools. To be able to produce standardized anti-human PcG antibodies, we developed a panel of five mouse monoclonal antibodies (MAbs) against the human PcG proteins HPC2, BMI1, RING1A, EED, and EZH2. All MAbs can be used for Western blot analysis and immunofluorescence labeling of tissue culture cells. With the exception of the MAb against HPC2, all MAbs can also be used in immunoprecipitation experiments and immunohistochemistry of human tissues. The novel MAbs are therefore valuable tools for the cell biological, biochemical, and pathological analysis of human PcG proteins.
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PMID:A panel of monoclonal antibodies against human polycomb group proteins. 1219 77

The intestinal stem cell fuels the highest rate of tissue turnover in the body and has been implicated in intestinal disease and cancer; understanding the regulatory mechanisms controlling intestinal stem cell physiology is of great importance. Here, we provide evidence that the transcription factor YY1 is essential for intestinal stem cell renewal. We observe that YY1 loss skews normal homeostatic cell turnover, with an increase in proliferating crypt cells and a decrease in their differentiated villous progeny. Increased crypt cell numbers come at the expense of Lgr5(+) stem cells. On YY1 deletion, Lgr5(+) cells accelerate their commitment to the differentiated population, exhibit increased levels of apoptosis, and fail to maintain stem cell renewal. Loss of Yy1 in the intestine is ultimately fatal. Mechanistically, YY1 seems to play a role in stem cell energy metabolism, with mitochondrial complex I genes bound directly by YY1 and their transcript levels decreasing on YY1 loss. These unappreciated YY1 functions broaden our understanding of metabolic regulation in intestinal stem cell homeostasis.
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PMID:YY1 is indispensable for Lgr5+ intestinal stem cell renewal. 2482 61

Gene expression (GE) analyses on blood samples from marathon and half-marathon runners have reported significant impacts on the immune and inflammatory systems. An ultra-marathon trail (UMT) represents a greater effort due to its more testing conditions. For the first time, we report the genome-wide GE profiling in a group of 16 runners participating in an 82 km UMT competition. We quantified their differential GE profile before and after the race using HuGene2.0st microarrays (Affymetrix Inc., California, US). The results obtained were decomposed by means of an independent component analysis (ICA) targeting independent expression modes. We observed significant differences in the expression levels of 5,084 protein coding genes resulting in an overrepresentation of 14% of the human biological pathways from the Kyoto Encyclopedia of Genes and Genomes database. These were mainly clustered on terms related with protein synthesis repression, altered immune system and infectious diseases related mechanisms. In a second analysis, 27 out of the 196 transcriptional regulators (TRs) included in the Open Regulatory Annotation database were overrepresented. Among these TRs, we identified transcription factors from the hypoxia-inducible factors (HIF) family EPAS1 (p< 0.01) and HIF1A (p<0.001), and others jointly described in the gluconeogenesis program such as HNF4 (p< 0.001), EGR1 (p<0.001), CEBPA (p< 0.001) and a highly specific TR, YY1 (p<0.01). The five independent components, obtained from ICA, further revealed a down-regulation of 10 genes distributed in the complex I, III and V from the electron transport chain. This mitochondrial activity reduction is compatible with HIF-1 system activation. The vascular endothelial growth factor (VEGF) pathway, known to be regulated by HIF, also emerged (p<0.05). Additionally, and related to the brain rewarding circuit, the endocannabinoid signalling pathway was overrepresented (p<0.05).
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PMID:Affected pathways and transcriptional regulators in gene expression response to an ultra-marathon trail: Global and independent activity approaches. 2902 36