Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of the ferric citrate transport genes of Escherichia coli K-12 involves a signalling cascade that starts at the cell surface and proceeds to the cytoplasm. Three specific proteins are involved: FecA in the outer membrane, FecR in the cytoplasmic membrane, and FecI in the cytoplasm. The binding of dinuclear ferric citrate to FecA causes substantial structural changes in FecA, triggering the signal cascade. The amino-proximal end of FecA interacts with the carboxy-proximal end of FecR in the periplasm. FecR then transmits the signal across the cytoplasmic membrane into the cytoplasm and activates the FecI sigma factor, which binds to the RNA polymerase core enzyme and directs the RNA polymerase to the promoter upstream of the fecABCDE transport genes to initiate transcription. Transcription of the fecIR regulatory genes and the fec transport genes is repressed by the Fur protein loaded with Fe(2+). Therefore, transcription of the fec transport genes is subjected to double control: cells first detect iron deficiency and respond by synthesis of the regulatory proteins FecI and FecR, which initiate transcription of the fec transport genes, provided ferric citrate is available. FecI belongs to the extracytoplasmic function sigma factors, which are widespread among bacteria. With the recent sequencing of complete microbial genomes, it has become apparent that the FecIRA cascade is now a paradigm for the regulatory control of FecI family sigmas in Gram-negative bacteria.
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PMID:Regulation of the FecI-type ECF sigma factor by transmembrane signalling. 1273 8

A chronic microcytosis and hypochromia without any iron deficiency were observed in an 11-year-old boy of French Caucasian origin. The same hematological findings were also found for his mother. No abnormal hemoglobin (Hb) was detected using isoelectric focusing, cation exchange liquid chromatography and reversed phase liquid chromatography of the globin chains but DNA sequencing revealed a CTG>CCG transition at codon 106 (Leu-->Pro) of the alpha1-globin gene in both of them. As the alpha/beta mRNA ratios, determined by reverse-transcriptase real-time quantitative polymerase chain reaction (PCR), are not concordant with an alpha-thalassemia (alpha-thal) state, we hypothesize that the underlying physiopathologic mechanism is an assembling defect of the Hb Charlieu molecule, rather than an instability of the alpha(Charlieu) mRNA. Moreover, genetic counseling and patient information are required in this family to prevent potentially severe alpha-thalassemias in following generations.
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PMID:Hb Charlieu [alpha106(G13)Leu-->Pro (alpha1)]: a new phenotypically silent hemoglobin variant associated with a mild alpha-thalassemia phenotype. 2064 34

Nonsense-mediated mRNA decay (NMD) prevents the accumulation of transcripts bearing premature termination codons. Here we show that Saccharomyces cerevisiae NMD mutants accumulate 5'-extended RNAs (CD-CUTs) of many subtelomeric genes. Using the subtelomeric ZRT1 and FIT3 genes activated in response to zinc and iron deficiency, respectively, we show that transcription of these CD-CUTs mediates repression at the bona fide promoters, by preventing premature binding of RNA polymerase II in conditions of metal repletion. Expression of the main ZRT1 CD-CUT is controlled by the histone deacetylase Rpd3p, showing that histone deacetylases can regulate expression of genes through modulation of the level of CD-CUTs. Analysis of binding of the transcriptional activator Zap1p and insertion of transcriptional terminators upstream from the Zap1p binding sites show that CD-CUT transcription or accumulation also interferes with binding of the transcriptional activator Zap1p. Consistent with this model, overexpressing Zap1p or using a constitutively active version of the Aft1p transcriptional activator rescues the induction defect of ZRT1 and FIT3 in NMD mutants. These results show that cryptic upstream sense transcription resulting in unstable transcripts degraded by NMD controls repression of a large number of genes located in subtelomeric regions, and in particular of many metal homeostasis genes.
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PMID:Cryptic transcription mediates repression of subtelomeric metal homeostasis genes. 2173 94

Poor iron status is a global health issue, affecting two thirds of the world population to some degree. It is a particular problem among pregnant women, in both developed and developing countries. Feeding pregnant rats a diet deficient in iron is associated with both hypertension and reduced nephron endowment in adult male offspring. However, the mechanistic pathway leading from iron deficiency to fetal kidney development remains elusive. This study aimed to establish the underlying processes associated with iron deficiency by assessing gene and protein expression changes in the rat embryo, focussing on the responses occurring at the time of the nutritional insult. Analysis of microarray data showed that iron deficiency in utero resulted in the significant up-regulation of 979 genes and down-regulation of 1545 genes in male rat embryos (d13). Affected processes associated with these genes included the initiation of mitosis, BAD-mediated apoptosis, the assembly of RNA polymerase II preinitiation complexes and WNT signalling. Proteomic analyses highlighted 7 proteins demonstrating significant up-regulation with iron deficiency and the down-regulation of 11 proteins. The main functions of these key proteins included cell proliferation, protein transport and folding, cytoskeletal remodelling and the proteasome complex. In line with our recent work, which identified the perturbation of the proteasome complex as a generalised response to in utero malnutrition, we propose that iron deficiency alone leads to a more specific failure in correct protein folding and transport. Such an imbalance in this delicate quality-control system can lead to cellular dysfunction and apoptosis. Therefore these findings offer an insight into the underlying mechanisms associated with the development of the embryo during conditions of poor iron status, and its health in adult life.
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PMID:Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat. 2311 Jan 88

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency.
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PMID:Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus. 2551 36