scholarly journals Key Function for the CCAAT-Binding Factor Php4 To Regulate Gene Expression in Response to Iron Deficiency in Fission Yeast

2008 ◽  
Vol 7 (3) ◽  
pp. 493-508 ◽  
Author(s):  
Alexandre Mercier ◽  
Stephen Watt ◽  
Jürg Bähler ◽  
Simon Labbé
Keyword(s):  
Iron Deficiency ◽  
Fission Yeast ◽  
Tricarboxylic Acid Cycle ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Gata Factor ◽  
Iron Starvation ◽  
A Genome ◽  
Binding Factor ◽  
Genes Encoding

ABSTRACT The fission yeast Schizosaccharomyces pombe responds to the deprivation of iron by inducing the expression of the php4 + gene, which encodes a negative regulatory subunit of the heteromeric CCAAT-binding factor. Once formed, the Php2/3/4/5 transcription complex is required to inactivate a subset of genes encoding iron-using proteins. Here, we used a pan-S. pombe microarray to study the transcriptional response to iron starvation and identified 86 genes that exhibit php4 + -dependent changes on a genome-wide scale. One of these genes encodes the iron-responsive transcriptional repressor Fep1, whose mRNA levels were decreased after treatment with the permeant iron chelator 2,2′-dipyridyl. In addition, several genes encoding the components of iron-dependent biochemical pathways, including the tricarboxylic acid cycle, mitochondrial respiration, amino acid biosynthesis, and oxidative stress defense, were downregulated in response to iron deficiency. Furthermore, Php4 repressed transcription when brought to a promoter using a yeast DNA-binding domain, and iron deprivation was required for this repression. On the other hand, Php4 was constitutively active when glutathione levels were depleted within the cell. Based on these and previous results, we propose that iron-dependent inactivation of Php4 is regulated at two distinct levels: first, at the transcriptional level by the iron-responsive GATA factor Fep1 and second, at the posttranscriptional level by a mechanism yet to be identified, which inhibits Php4-mediated repressive function when iron is abundant.

scholarly journals Transcriptional regulation by glucocorticoids of mitochondrial oxidative enzyme genes in the developing rat kidney

1996 ◽  
Vol 315 (2) ◽  
pp. 555-562 ◽  
Author(s):  
Fatima DJOUADI ◽  
Jean BASTIN ◽  
Daniel P. KELLY ◽  
Claudie MERLET-BENICHOU
Keyword(s):  
Fatty Acid ◽  
Molecular Mechanisms ◽  
Tricarboxylic Acid Cycle ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Transcriptional Level ◽  
Mitochondrial Enzymes ◽  
Mrna Levels ◽  
Rat Kidney Cortex ◽  
Mitochondrial Fatty Acid

Mitochondrial fatty acid β-oxidation plays a major role in providing the ATP required for reabsorptive processes in the adult rat kidney. However, the molecular mechanisms and signals involved in induction of the enzymes of fatty acid oxidation during development in this and other organs are unknown. We therefore studied the changes in the steady-state levels of mRNA encoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyses the initial step in mitochondrial fatty acid β-oxidation, in the rat kidney cortex and medulla between postnatal days 10 and 30. Furthermore, we investigated whether the expression of MCAD and of mitochondrial malate dehydrogenase (mMDH), a key enzyme in the tricarboxylic acid cycle, might be co-ordinately regulated by circulating glucocorticoids in the immature kidney during development. In the cortex, the levels of MCAD mRNA rose 4-fold between day 10 and day 21, and then decreased from day 21 to day 30. In the medulla a postnatal increase in the concentration of MCAD mRNA (8-fold) was observed during the same period. Adrenalectomy prevented the 16–21-day developmental increases in MCAD and mMDH mRNA levels in the cortex and medulla; these could be restored by dexamethasone treatment. A single injection of dexamethasone into 10-day-old rats led to a rise in MCAD and mMDH mRNA levels in the renal cortex due to stimulation of gene transcription, as shown by nuclear run-on assays. Therefore MCAD and mMDH gene expression is tightly regulated at the transcriptional level by developmental changes in circulating glucocorticoid levels. These hormones might thus represent a good candidate as a co-ordinating factor in the expression of nuclear genes encoding mitochondrial enzymes in the kidney during postnatal development.

scholarly journals Regulation of freA, acoA, lysF, and cycA Expression by Iron Availability in Aspergillus nidulans

2002 ◽  
Vol 68 (11) ◽  
pp. 5769-5772 ◽  
Author(s):  
Harald Oberegger ◽  
Michelle Schoeser ◽  
Ivo Zadra ◽  
Markus Schrettl ◽  
Walther Parson ◽  
...  
Keyword(s):  
Aspergillus Nidulans ◽  
Iron Homeostasis ◽  
Regulatory Mechanism ◽  
Growth Conditions ◽  
Iron Limitation ◽  
Transcriptional Level ◽  
Iron Availability ◽  
Gata Factor ◽  
Genes Encoding ◽  
Encoding Gene

ABSTRACT In the filamentous fungus Aspergillus nidulans, iron homeostasis is regulated at the transcriptional level by the negative-acting GATA factor SREA. In this study the expression of a putative heme-containing metalloreductase-encoding gene, freA, was found to be upregulated by iron limitation independently of SREA, demonstrating the existence of an iron-regulatory mechanism which does not involve SREA. In contrast to freA, various other genes encoding proteins in need of iron-containing cofactors—acoA, lysF, and cycA—were downregulated in response to iron depletion. Remarkably, SREA deficiency led to increased expression of acoA, lysF, and cycA under iron-replete growth conditions.

Isolation and characterization of a cDNA encoding an ACC oxidase from Cicer arietinum and its expression during embryogenesis and seed germination

1998 ◽  
Vol 25 (6) ◽  
pp. 765 ◽  
Author(s):  
M.C. Gómez-Jiménez ◽  
A.J. Matilla ◽  
D. Garrido
Keyword(s):  
Molecular Weight ◽  
Cicer Arietinum ◽  
Acc Oxidase ◽  
Protein Product ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Embryonic Axes ◽  
Chick Pea ◽  
Isolation And Characterization ◽  
Genes Encoding

A full length cDNA (caaco1) encoding a putative ACC-oxidase (ACCO) was isolated and sequenced from embryonic axes of chick-pea (Cicer arietinum L.) seeds, which depend on ethylene synthesis for germination. The deduced protein for caaco1 has a molecular weight of 36 kDa, a high homology with other ACCOs and is apparently found in the cytosolic fraction of the cell. Heterologous expression of this cDNA confirmed that the protein product exhibits ACCO activity and a molecular weight close to 38 kDa. Southern blot analysis shows that there are at least two genes encoding ACCO in the chick-pea genome. The caaco1 mRNA levels in seeds remained constant during the initial stages of embryogenesis decreasing in the latest stages. During germination, caaco1 mRNA levels increase, reaching a maximum at 24 h, coinciding with the maximum percentage of germination (when all seeds are germinated), ACCO activity and ethylene production. It is interesting that there is a shift in the tissue source of the caaco1 mRNA during embryogenesis and germination. While the bulk of the expression was detected in cotyledons during embryogenesis, it was the embryonic axis that provided most of the expression detected during germination. Our data suggest that during embryogenesis ACCO is regulated at the translational level, but during germination at the transcriptional level.

scholarly journals A Transcription Factor Cascade Involving Fep1 and the CCAAT-Binding Factor Php4 Regulates Gene Expression in Response to Iron Deficiency in the Fission Yeast Schizosaccharomyces pombe

2006 ◽  
Vol 5 (11) ◽  
pp. 1866-1881 ◽  
Author(s):  
Alexandre Mercier ◽  
Benoit Pelletier ◽  
Simon Labbé
Keyword(s):  
Schizosaccharomyces Pombe ◽  
Transcriptional Activation ◽  
Tricarboxylic Acid Cycle ◽  
Site Directed Mutagenesis ◽  
Regulatory Subunit ◽  
Regulatory Sequence ◽  
Mrna Levels ◽  
Rnase Protection ◽  
Iron Storage ◽  
Binding Factor

ABSTRACT We have identified genes encoding candidate proteins involved in iron storage (pcl1 + ), the tricarboxylic acid cycle (sdh4 + ), and iron-sulfur cluster assembly (isa1 + ) that are negatively regulated in response to iron deprivation. Promoter deletion and site-directed mutagenesis permitted identification of a new cis-regulatory element in the promoter region of the pcl1 + gene. This cis-acting regulatory sequence containing the pentanucleotide sequence CCAAT is responsible for transcriptional repression of pcl1 + under low iron supply conditions. In Schizosaccharomyces pombe, the CCAAT-binding factor is a heteromeric DNA-binding complex that contains three subunits, designated Php2, Php3, and Php5. Inactivation of the php2 + locus negatively affects the transcriptional competency of pcl1 + . A fourth subunit, designated Php4, is not essential for the transcriptional activation of target genes under basal and iron-replete conditions. We demonstrate that, in response to iron-limiting conditions, Php4 is required for down-regulation of pcl1 + , sdh4 + , and isa1 + mRNA levels. In vivo RNase protection studies reveal that the expression of php4 + is negatively regulated by iron and that this regulated expression requires a functional fep1 + gene. The results of these studies reveal that Fep1 represses php4 + expression in response to iron. In contrast, when iron is scarce, Fep1 becomes inactive and php4 + is expressed to act as a regulatory subunit of the CCAAT-binding factor that is required to block pcl1 + , sdh4 + , and isa1 + gene transcription.

scholarly journals Proteomic and Transcriptomic Analysis of Extracellular Proteins and mRNA Levels in Thermobifida fusca Grown on Cellobiose and Glucose

2007 ◽  
Vol 189 (17) ◽  
pp. 6260-6265 ◽  
Author(s):  
Shaolin Chen ◽  
David B. Wilson
Keyword(s):  
Cell Wall ◽  
Plant Cell Wall ◽  
Extracellular Proteins ◽  
Transcriptional Analysis ◽  
Thermobifida Fusca ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Egg White Lysozyme ◽  
Extracellular Proteome ◽  
Genes Encoding

ABSTRACT Thermobifida fusca secretes proteins that carry out plant cell wall degradation. Using two-dimensional electrophoresis, the extracellular proteome of T. fusca grown on cellobiose was compared to that of cells grown on glucose. Extracellular proteins, the expression of which is induced by cellobiose, mainly are cellulases and cellulose-binding proteins. Other major extracellular proteins induced by cellobiose include a xylanase (Xyl10A) and two unknown proteins, the C-terminal regions of which are homologous to a lytic transglycosylase goose egg white lysozyme domain and an NLPC_P60 domain (which defines a family of cell wall peptidases), respectively. Transcriptional analysis of genes encoding cellobiose-induced proteins suggests that their expression is controlled at the transcriptional level and that their expression also is induced by cellulose. Some other major extracellular proteins produced by T. fusca grown on both cellobiose and glucose include Lam81A and three unknown proteins that are homologous to aminopeptidases and xylanases or that contain a putative NLPC_P60 domain.

scholarly journals Genome-wide expression analysis identifies core components during iron starvation in hexaploid wheat

2019 ◽  
Author(s):  
Gazaldeep Kaur ◽  
Vishnu Shukla ◽  
Anil Kumar ◽  
Mandeep Kaur ◽  
Parul Goel ◽  
...  
Keyword(s):  
Hexaploid Wheat ◽  
Design Strategies ◽  
Glutathione S Transferase ◽  
Iron Starvation ◽  
Wheat Roots ◽  
Metal Transporters ◽  
Genome Wide ◽  
A Genome ◽  
Genes Encoding ◽  
Yellow Stripe

AbstractIron is one of essential micronutrient for all organisms. Its deficiency causes a severe loss in crops yield. Nevertheless, our current understanding on major crops response to Fe deficiency remains limited. Herein, we investigated the effect of Fe deprivation at both transcriptomic and metabolic levels in hexaploid wheat. A genome-wide gene expression reprogramming was observed with a total of 5854 genes showing differential expression in roots of wheat subjected to Fe-starved medium. Subsequent, analysis revealed a predominance of strategy-II mode of Fe uptake, with induced genome bias contribution from the A and B genomes. In general, the predominance of genes encoding for nicotianamine synthase, yellow stripe like transporters, metal transporters, ABC transporters and zinc-induced facilitator-like protein was noticed. Our transcriptomic data were in agreement with the GC-MS analysis that showed an enhancement of accumulation of various metabolites such as fumarate, malonate, succinate and xylofuranose, which could be linked for enhancing Fe-mobilization. Interestingly, Fe starvation causes a significant temporal increase of glutathione-S-transferase both at transcriptional and enzymatic activity, which indicate the important role of glutathione in the response to Fe starvation in wheat roots. Taken together, our result provides new insight on wheat response to Fe starvation and lays foundation to design strategies to improve Fe nutrition in crops.

scholarly journals Altered transcriptome-proteome coupling indicates aberrant proteostasis in Parkinson’s disease

2021 ◽  
Author(s):  
Fiona Dick ◽  
Ole-Bjørn Tysnes ◽  
Guido Werner Alves ◽  
Gonzalo S. Nido ◽  
Charalampos Tzoulis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Level ◽  
Spatial Separation ◽  
Healthy Ageing ◽  
Mrna Levels ◽  
Protein Levels ◽  
A Genome ◽  
Genes Encoding ◽  
Ageing Brain

AbstractThe correlation between mRNA and protein levels has been shown to decline in the ageing brain, possibly reflecting age-dependent changes in the proteostasis. It is thought that impaired proteostasis may be implicated in the pathogenesis of Parkinson’s disease (PD), but evidence derived from the patient brain is currently limited. Here, we hypothesized that if impaired proteostasis occurs in PD, this should be reflected in the form of altered correlation between transcriptome and proteome compared to healthy ageing.To test this hypothesis, we integrated transcriptomic data with proteomics from prefrontal cortex tissue of 17 PD patients and 11 demographically matched healthy controls and assessed gene-specific correlations between RNA and protein level. To control for the effects of ageing, brain samples from 4 infants were included in the analyses.In the healthy aged brain, we observed a genome-wide decreased correlation between mRNA and protein levels. Moreover, a group of genes encoding synaptic vesicle proteins exhibited inverse correlations. This phenomenon likely reflects the spatial separation of mRNA and protein into the neuronal soma and synapsis, respectively, commonly characterizing these genes. Most genes showed a significantly lower correlation between mRNA and protein levels in PD compared to neurologically healthy ageing, consistent with a proteome-wide decline in proteostasis. Genes showing an inverse correlation in PD were enriched for proteasome subunits, suggesting that these proteins show accentuated spatial separation of transcript and protein between the soma and axon/synapses in PD neurons. Moreover, the PD brain was characterized by increased positive mRNA-protein correlation for some genes encoding components of the mitochondrial respiratory chain, suggesting these may require tighter regulation in the face of mitochondrial pathology characterizing the PD brain.Our results are highly consistent with a proteome-wide impairment of proteostasis in the PD brain and strongly support the hypothesis that aberrant proteasomal function is implicated in the pathogenesis of PD. Moreover, our findings have important implications for the correct interpretation of differential gene expression studies in PD. In the presence of disease-specific altered coupling of transcriptome and proteome, measured differences in mRNA levels cannot be used to infer changes at the protein-level and should be supplemented with direct determination of proteins nominated by the analyses.

Expression of the atf1+ gene is upregulated in fission yeast under nitrosative and nutritional stresses

2009 ◽  
Vol 55 (11) ◽  
pp. 1323-1327 ◽  
Author(s):  
S.-H. Song ◽  
B.-M. Kim ◽  
C.-J. Lim ◽  
Y.S. Song ◽  
E.-H. Park
Keyword(s):  
Nitric Oxide ◽  
Schizosaccharomyces Pombe ◽  
Sodium Nitroprusside ◽  
Fission Yeast ◽  
Fusion Gene ◽  
Lacz Fusion ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Nitrogen Depletion ◽  
Rt Pcr

This work was designed to assess regulation of the atf1+ gene in the fission yeast Schizosaccharomyces pombe under nitrosative and nutritional stresses, using the atf1+–lacZ fusion gene and RT–PCR. Nitric oxide (NO)-generating sodium nitroprusside (SNP; 10 µmol/L) and nitrogen depletion significantly enhanced synthesis of β-galactosidase from the atf1+–lacZ fusion gene in S. pombe Pap1-positive KP1 cells, but not in S. pombe Pap1-negative TP108-3C cells. SNP (10 µmol/L) and nitrogen depletion also caused a significant increase in atf1+ mRNA levels in Pap1-positive cells, but not in Pap1-negative cells. Depletion of glucose marginally increased synthesis of β-galactosidase from the fusion gene in S. pombe Pap1-positive cells. Taken together, the S. pombe atf1+ gene is upregulated by nitrosative and nutritional stresses on a transcriptional level, possibly via the mediation of Pap1.

scholarly journals Differential Influence of Inositol Hexaphosphate on the Expression of Genes Encoding TGF-βIsoforms and Their Receptors in Intestinal Epithelial Cells Stimulated with Proinflammatory Agents

2013 ◽  
Vol 2013 ◽  
pp. 1-10
Author(s):  
Małgorzata Kapral ◽  
Joanna Wawszczyk ◽  
Stanisław Sośnicki ◽  
Ludmiła Węglarz
Keyword(s):  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Inflammatory Responses ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Inositol Hexaphosphate ◽  
Inflammatory Conditions ◽  
Expression Of Genes ◽  
Genes Encoding

Transforming growth factorβ(TGF-β) is a multifunctional cytokine recognized as an important regulator of inflammatory responses. The effect of inositol hexaphosphate (IP6), a naturally occurring phytochemical, on the mRNA expression of TGF-β1, TGF-β2, TGF-β3 and TβRI, TβRII, and TβRIII receptors stimulated with bacterial lipopolysaccharides (Escherichia coliandSalmonella typhimurium) and IL-1βin intestinal cells Caco-2 for 3 and 12 h was investigated. Real-time qRT-PCR was used to validate mRNAs level of examined genes. Bacterial endotoxin promoted differential expression of TGF-βs and their receptors in a time-dependent manner. IL-1βupregulated mRNA levels of all TGF-βs and receptors at both 3 h and 12 h. IP6 elicited the opposed to LPS effect by increasing downregulated transcription of the examined genes and suppressing the expression of TGF-β1 at 12 h. IP6 counteracted the stimulatory effect of IL-1βon TGF-β1 and receptors expression by decreasing their mRNA levels. IP6 enhanced LPS- and IL-1β-stimulated mRNA expression of TGF-β2 and -β3. Based on these studies it may be concluded that IP6 present in the intestinal milieu may exert immunoregulatory effects and chemopreventive activity on colonic epithelium under inflammatory conditions or during microbe-induced infection/inflammation by modulating the expression of genes encoding TGF-βs and their receptors at transcriptional level.

Endotoxin-Induced Tissue Factor in Human Monocytes is Dependent upon Protein Kinase C Activation

1993 ◽  
Vol 70 (05) ◽  
pp. 800-806 ◽  
Author(s):  
C Ternisien ◽  
M Ramani ◽  
V Ollivier ◽  
F Khechai ◽  
T Vu ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tissue Factor ◽  
Factor Ix ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Kinase C ◽  
Pkc Activation

SummaryTissue factor (TF) is a transmembrane receptor which, in association with factors VII and Vila, activates factor IX and X, thereby activating the coagulation protease cascades. In response to bacterial lipopolysaccharide (LPS) monocytes transcribe, synthesize and express TF on their surface. We investigated whether LPS-induced TF in human monocytes is mediated by protein kinase C (PKC) activation. The PKC agonists phorbol 12- myristate 13-acetate (PMA) and phorbol 12, 13 dibutyrate (PdBu) were both potent inducers of TF in human monocytes, whereas 4 alpha-12, 13 didecanoate (4 a-Pdd) had no such effect. Both LPS- and PMA-induced TF activity were inhibited, in a concentration dependent manner, by three different PKC inhibitors: H7, staurosporine and calphostin C. TF antigen determination confirmed that LPS-induced cell-surface TF protein levels decreased in parallel to TF functional activity under staurosporine treatment. Moreover, Northern blot analysis of total RNA from LPS- or PMA-stimulated monocytes showed a concentration-dependent decrease in TF mRNA levels in response to H7 and staurosporine. The decay rate of LPS-induced TF mRNA evaluated after the arrest of transcription by actinomycin D was not affected by the addition of staurosporine, suggesting that its inhibitory effect occurred at a transcriptional level. We conclude that LPS-induced production of TF and its mRNA by human monocytes are dependent on PKC activation.

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