scholarly journals A Regulatory Circuit Composed of a Transcription Factor, IscR, and a Regulatory RNA, RyhB, Controls Fe-S Cluster Delivery

mBio ◽  
2016 ◽  
Vol 7 (5) ◽  
Author(s):  
Pierre Mandin ◽  
Sylvia Chareyre ◽  
Frédéric Barras
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Mutational Analysis ◽  
Essential Gene ◽  
Iron Concentration ◽  
Transcriptional Level ◽  
Iron Starvation ◽  
Control Of Gene Expression ◽  
Regulatory Circuit ◽  
Iron Concentrations

ABSTRACT Fe-S clusters are cofactors conserved through all domains of life. Once assembled by dedicated ISC and/or SUF scaffolds, Fe-S clusters are conveyed to their apo-targets via A-type carrier proteins (ATCs). Escherichia coli possesses four such ATCs. ErpA is the only ATC essential under aerobiosis. Recent studies reported a possible regulation of the erpA mRNA by the small RNA (sRNA) RyhB, which controls the expression of many genes under iron starvation. Surprisingly, erpA has not been identified in recent transcriptomic analysis of the iron starvation response, thus bringing into question the actual physiological significance of the putative regulation of erpA by RyhB. Using an sRNA library, we show that among 26 sRNAs, only RyhB represses the expression of an erpA-lacZ translational fusion. We further demonstrate that this repression occurs during iron starvation. Using mutational analysis, we show that RyhB base pairs to the erpA mRNA, inducing its disappearance. In addition, IscR, the master regulator of Fe-S homeostasis, represses expression of erpA at the transcriptional level when iron is abundant, but depleting iron from the medium alleviates this repression. The conjunction of transcriptional derepression by IscR and posttranscriptional repression by RyhB under Fe-limiting conditions is best described as an incoherent regulatory circuit. This double regulation allows full expression of erpA at iron concentrations for which Fe-S biogenesis switches from the ISC to the SUF system. We further provide evidence that this regulatory circuit coordinates ATC usage to iron availability. IMPORTANCE Regulatory small RNAs (sRNAs) have emerged as major actors in the control of gene expression in the last few decades. Relatively little is known about how these regulators interact with classical transcription factors to coordinate genetic responses. We show here how an sRNA, RyhB, and a transcription factor, IscR, regulate expression of an essential gene, erpA , in the bacterium E. coli . ErpA is involved in the biogenesis of Fe-S clusters, an important class of cofactors involved in a plethora of cellular reactions. Interestingly, we show that RyhB and IscR repress expression of erpA under opposite conditions in regard to iron concentration, forming a regulatory circuit called an “incoherent network.” This incoherent network serves to maximize expression of erpA at iron concentrations where it is most needed. Altogether, our study paves the way for a better understanding of mixed regulatory networks composed of RNAs and transcription factors.

scholarly journals The Regulatory Mechanism of Water Activities on Aflatoxins Biosynthesis and Conidia Development, and Transcription Factor AtfB Is Involved in This Regulation

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 431
Author(s):  
Longxue Ma ◽  
Xu Li ◽  
Xiaoyun Ma ◽  
Qiang Yu ◽  
Xiaohua Yu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Environmental Factors ◽  
Health Risks ◽  
Sexual Development ◽  
Regulatory Mechanism ◽  
Food Storage ◽  
Economic Losses ◽  
Transcriptional Level ◽  
Conidia Production

Peanuts are frequently infected by Aspergillus strains and then contaminated by aflatoxins (AF), which brings out economic losses and health risks. AF production is affected by diverse environmental factors, especially water activity (aw). In this study, A. flavus was inoculated into peanuts with different aw (0.90, 0.95, and 0.99). Both AFB1 yield and conidia production showed the highest level in aw 0.90 treatment. Transcriptional level analyses indicated that AF biosynthesis genes, especially the middle- and later-stage genes, were significantly up-regulated in aw 0.90 than aw 0.95 and 0.99. AtfB could be the pivotal regulator response to aw variations, and could further regulate downstream genes, especially AF biosynthesis genes. The expressions of conidia genes and relevant regulators were also more up-regulated at aw 0.90 than aw 0.95 and 0.99, suggesting that the relative lower aw could increase A. flavus conidia development. Furthermore, transcription factors involved in sexual development and nitrogen metabolism were also modulated by different aw. This research partly clarified the regulatory mechanism of aw on AF biosynthesis and A. flavus development and it would supply some advice for AF prevention in food storage.

scholarly journals The histone H3K4 demethylase JARID1A directly interacts with haematopoietic transcription factor GATA1 in erythroid cells through its second PHD domain

2020 ◽  
Vol 7 (1) ◽  
pp. 191048 ◽  
Author(s):  
Dimple Karia ◽  
Robert C. G. Gilbert ◽  
Antonio J. Biasutto ◽  
Catherine Porcher ◽  
Erika J. Mancini
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Blood Cells ◽  
Physical Contact ◽  
Histone Demethylases ◽  
Control Of Gene Expression ◽  
Histone H3k4 ◽  
Lineage Specific Genes ◽  
Phd Domain

Chromatin remodelling and transcription factors play important roles in lineage commitment and development through control of gene expression. Activation of selected lineage-specific genes and repression of alternative lineage-affiliated genes result in tightly regulated cell differentiation transcriptional programmes. However, the complex functional and physical interplay between transcription factors and chromatin-modifying enzymes remains elusive. Recent evidence has implicated histone demethylases in normal haematopoietic differentiation as well as in malignant haematopoiesis. Here, we report an interaction between H3K4 demethylase JARID1A and the haematopoietic-specific master transcription proteins SCL and GATA1 in red blood cells. Specifically, we observe a direct physical contact between GATA1 and the second PHD domain of JARID1A. This interaction has potential implications for normal and malignant haematopoiesis.

scholarly journals Activation of codependent transcription factors is required for transcriptional induction of the vgf gene by nerve growth factor and Ras.

1996 ◽  
Vol 16 (9) ◽  
pp. 4621-4631 ◽  
Author(s):  
G D'Arcangelo ◽  
R Habas ◽  
S Wang ◽  
S Halegoua ◽  
S R Salton
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Pc12 Cells ◽  
Mutational Analysis ◽  
Globin Gene ◽  
Beta Globin ◽  
Nerve Growth ◽  
Transcriptional Induction

Nerve growth factor (NGF) treatment of PC12 cells leads to the elaboration of a neuronal phenotype, including the induction of neuronally expressed genes such as vgf. To study vgf transcription, we have created chimeric vgf/beta-globin genes in which vgf promoter sequences drive the expression of the beta-globin reporter gene or of a chimeric beta-globin gene fused to 3' untranslated vgf gene sequences. We have found that the level of inducibility of the latter construct by NGF resembles that of the endogenous vgf gene. Using transient transfection of the chimeric reporter genes into PC12 cells, into PC12 subclones expressing activated or dominantly interfering mutant Ras proteins, and into PC12 variants expressing specific NGF receptor/Trk mutants, we show that transcriptional regulation of the vgf promoter by NGF is mediated through a Ras-dependent signaling pathway. By mutational analysis of the vgf promoter, we have identified three promoter elements involved in mediating transcriptional induction by NGF and Ras. In addition to the cyclic AMP-responsive element (CRE), which binds to ATF-1, ATF-2, and CRE-binding protein in PC12 nuclear extracts, a novel CCAAT element and its binding proteins were identified, which, like the CRE, is necessary but not sufficient for the Ras-dependent induction of the vgf gene by NGF. We also identify a G(S)G element unusually located between the TATA box and transcriptional start site, which binds the NGF- and Ras-induced transcription factor, NGFI-A, and amplifies the transcriptional response. Integrating data from studies of vgf promoter regulation and NGF signal transduction, we present a model for vgf gene induction in which transcriptional activation is achieved through the persistent, direct activation of multiple interacting transcription factors binding to CRE and CCAAT elements, coordinated with the delayed transcription factor action at a G(S)G element resulting from the induced expression of NGFI-A.

scholarly journals ACE4, a novel transcriptional activator involved in the regulation of cellulase genes on cellulose in Trichoderma reesei

2021 ◽  
Author(s):  
Yumeng Chen ◽  
Aibo Lin ◽  
Pei Liu ◽  
Xingjia Fan ◽  
Chuan Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Trichoderma Reesei ◽  
Transcriptional Activator ◽  
Cellulase Production ◽  
Comparative Genomic ◽  
Transcriptional Level ◽  
Cellulase Gene ◽  
Cellulase Expression

The filamentous fungus Trichoderma reesei is a model strain for cellulase production. Cellulase gene expression in T. reesei is controlled by multiple transcription factors. Here, we identified by comparative genomic screening a novel transcriptional activator ACE4 ( A ctivator of c ellulase e xpression 4) that positively regulates cellulase gene expression on cellulose in T. reesei . Disruption of the ace4 gene significantly decreased expression of four main cellulase genes, and the essential cellulase transcription factor encoding gene ace3 . Overexpression of ace4 increased cellulase production by approximately 22% compared to that in the parental strain. Further investigations using electrophoretic mobility shift assays, DNase I footprinting assays, and chromatin immunoprecipitation assays indicated that ACE4 directly binds to the promoter of cellulase genes by recognizing the two adjacent 5′-GGCC-3′ sequences. Additionally, ACE4 directly binds to the promoter of ace3 and, in turn, regulates the expression of ACE3 to facilitate cellulase production. Collectively, these results demonstrate an important role for ACE4 in regulating cellulase gene expression, which will contribute to understanding the mechanism underlying cellulase expression in T. reesei . IMPORTANCE T. reesei is commonly utilized in industry to produce cellulases, enzymes that degrade lignocellulosic biomass for the production of bioethanol and bio-based products. T. reesei is capable of rapidly initiating the biosynthesis of cellulases in the presence of cellulose, which has made it useful as a model fungus for studying gene expression in eukaryotes. Cellulase gene expression is controlled through multiple transcription factors at the transcriptional level. However, the molecular mechanisms by which transcription is controlled remain unclear. In the present study, we identified a novel transcription factor, ACE4, which regulates cellulase expression on cellulose by binding to the promoters of cellulase genes and the cellulase activator ace3 . Our study not only expands the general functional understanding of the novel transcription factor ACE4 but also provides evidence for the regulatory mechanism mediating gene expression in T. reesei .

scholarly journals Broad-Spectrum HDAC Inhibitors Promote Autophagy through FOXO Transcription Factors in Neuroblastoma

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1001
Author(s):  
Katharina Körholz ◽  
Johannes Ridinger ◽  
Damir Krunic ◽  
Sara Najafi ◽  
Xenia F. Gerloff ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Tumor Growth ◽  
Broad Spectrum ◽  
Nuclear Translocation ◽  
Hdac Inhibitors ◽  
Neuroblastoma Cells ◽  
Autophagic Flux ◽  
Transcriptional Level ◽  
Hdaci Treatment

Depending on context and tumor stage, deregulation of autophagy can either suppress tumorigenesis or promote chemoresistance and tumor survival. Histone deacetylases (HDACs) can modulate autophagy; however, the exact mechanisms are not fully understood. Here, we analyze the effects of the broad-spectrum HDAC inhibitors (HDACi) panobinostat and vorinostat on the transcriptional regulation of autophagy with respect to autophagy transcription factor activity (Transcription factor EB—TFEB, forkhead boxO—FOXO) and autophagic flux in neuroblastoma cells. In combination with the late-stage autophagic flux inhibitor bafilomycin A1, HDACis increase the number of autophagic vesicles, indicating an increase in autophagic flux. Both HDACi induce nuclear translocation of the transcription factors FOXO1 and FOXO3a, but not TFEB and promote the expression of pro-autophagic FOXO1/3a target genes. Moreover, FOXO1/3a knockdown experiments impaired HDACi treatment mediated expression of autophagy related genes. Combination of panobinostat with the lysosomal inhibitor chloroquine, which blocks autophagic flux, enhances neuroblastoma cell death in culture and hampers tumor growth in vivo in a neuroblastoma zebrafish xenograft model. In conclusion, our results indicate that pan-HDACi treatment induces autophagy in neuroblastoma at a transcriptional level. Combining HDACis with autophagy modulating drugs suppresses tumor growth of high-risk neuroblastoma cells. These experimental data provide novel insights for optimization of treatment strategies in neuroblastoma.

Role of SCL/Tal-1, GATA, and Ets transcription factor binding sites for the regulation of Flk-1 expression during murine vascular development

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3078-3085 ◽  
Author(s):  
Andreas Kappel ◽  
Thorsten M. Schlaeger ◽  
Ingo Flamme ◽  
Stuart H. Orkin ◽  
Werner Risau ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Blood Vessel ◽  
Tumor Angiogenesis ◽  
Binding Sites ◽  
Mutational Analysis ◽  
Vascular Development ◽  
Regulatory Elements ◽  
Specific Expression ◽  
Ets Transcription Factors

The receptor tyrosine kinase Flk-1 is essential for embryonic blood vessel development and for tumor angiogenesis. To identify upstream transcriptional regulators of Flk-1, the gene regulatory elements that mediate endothelium-specific expression in mouse embryos were characterized. By mutational analysis, binding sites for SCL/Tal-1, GATA, and Ets transcription factors located in theFlk-1 enhancer were identified as critical elements for the endothelium-specific Flk-1 gene expression in transgenic mice. c-Ets1, a transcription factor that is coexpressed withFlk-1 during embryonic development and tumor angiogenesis, activated the Flk-1 promoter via 2 binding sites. One of these sites was required for Flk-1 promoter function in the embryonic vasculature. These results provide the first evidence that SCL/Tal-1, GATA, and Ets transcription factors act upstream ofFlk-1 in a combinatorial fashion to determine embryonic blood vessel formation and are key regulators not only of the hematopoietic program, but also of vascular development.

scholarly journals Integrated Nuclear Proteomics and Transcriptomics Identifies New High Frequency Dysregulated Transcription Factors in AML

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3554-3554
Author(s):  
Chinmay R Munje ◽  
Andrew J. K. Williamson ◽  
Samuel Taylor ◽  
Robert K. Hills ◽  
Steven Knapper ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Experimental Design ◽  
Protein Identification ◽  
Target Genes ◽  
Conflicts Of Interest ◽  
Mrna Level ◽  
Transcriptional Level ◽  
Cd34 Cells ◽  
Nuclear Proteome

Abstract Acute myeloid leukemia (AML) is characterized by developmental arrest which is thought to arise from transcriptional dysregulation of myeloid development programs. Transcription factor (TF) dysregulation has been identified at both the genomic and transcriptomic levels; however the actual transcriptional environment in AML patients characterized by the relative abundance of TF protein expression compared with normal blasts has not yet been described. Here, we have analysed the nuclear proteome of AML blasts in comparison with normal CD34+ cells and carried out a parallel analysis of the transcriptome using Affymetrix arrays. In our experimental design we restricted our analysis to the minimally differentiated FAB M1 since this subtype has little developmental heterogeneity and would also be developmentally matched to normal controls. The final experimental design comprised nuclear protein extracts from 5 normal CD34+ controls and 15 FAB M1 patients (>80% viable blasts; <10% CD14+/CD15+ cells). Purity of nuclear fractions was assessed by western blotting for histone and GAPDH (Figure 1). Nuclear tryptic peptides were generated and in each experiment labelled with 8 channel isobaric tagging to allow relative quantification coupled with peptide/protein identification using tandem mass spectrometry. In parallel mRNA from these samples were analysed using Human Transcriptome Array 2.0 (Affymetrix, USA). In total 6164 proteins were found and quantified. After applying appropriate quality control criteria 437 proteins were found to be significantly dysregulated between normal CD34+ cells and AML blasts. To identify frequently dysregulated proteins we selected those that consistently changed in at least 5 AML patients (± >1.2 fold). This yielded 188 proteins of which 112 (60%) were nuclear proteins. We identified 7 upregulated transcription factors in leukaemic cells compared to normal CD34+ cells; 3 of which had been previously associated with AML (CEBPA, STAT6 and WT1). Comparative analysis of mRNA of these changes showed that these increases were also significantly observed at the transcriptional level (Table 1). The remainder (DRAP1, NFIC, HMGB1 and HMGB2) had not been previously reported in AML, and none of the changes were seen at the transcriptional level indicating increased expression arose at post-transcriptionally or were due to an increased level of nuclear localization. We also identified 7 down-regulated TF, one of which had been previously associated with AML (DAZAP1) with the remaining being newly described abnormalities (MYEF2, NFIX, FUBP1, TARDBP, ILF2, ILF3). Again most of these changes (4 of 6) were not seen at the transcriptional level. We also observed changes in 15 heterogeneous nuclear ribonucleoproteins (hnRNP) affecting mRNA processing (including: A0, A1, A2B1, A3, AB, C, D, DL, PF, H1, H3, K, L, R and UL2) and we are currently examining whether their expression correlates with increased alternative splicing that we have observed in these patients from analysis of the exon arrays. These data are the first analysis of the nuclear proteome in AML and have identified changes in transcription factor expression that would not have been seen at the mRNA level. We are performing in silico analysis to determine whether dysregulation of these TF give rise to corresponding changes in known target genes. Disclosures No relevant conflicts of interest to declare.

Role of SCL/Tal-1, GATA, and Ets transcription factor binding sites for the regulation of Flk-1 expression during murine vascular development

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3078-3085 ◽  
Author(s):  
Andreas Kappel ◽  
Thorsten M. Schlaeger ◽  
Ingo Flamme ◽  
Stuart H. Orkin ◽  
Werner Risau ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Blood Vessel ◽  
Tumor Angiogenesis ◽  
Binding Sites ◽  
Mutational Analysis ◽  
Vascular Development ◽  
Regulatory Elements ◽  
Specific Expression ◽  
Ets Transcription Factors

Abstract The receptor tyrosine kinase Flk-1 is essential for embryonic blood vessel development and for tumor angiogenesis. To identify upstream transcriptional regulators of Flk-1, the gene regulatory elements that mediate endothelium-specific expression in mouse embryos were characterized. By mutational analysis, binding sites for SCL/Tal-1, GATA, and Ets transcription factors located in theFlk-1 enhancer were identified as critical elements for the endothelium-specific Flk-1 gene expression in transgenic mice. c-Ets1, a transcription factor that is coexpressed withFlk-1 during embryonic development and tumor angiogenesis, activated the Flk-1 promoter via 2 binding sites. One of these sites was required for Flk-1 promoter function in the embryonic vasculature. These results provide the first evidence that SCL/Tal-1, GATA, and Ets transcription factors act upstream ofFlk-1 in a combinatorial fashion to determine embryonic blood vessel formation and are key regulators not only of the hematopoietic program, but also of vascular development.

scholarly journals Effect of repetitive icv injections of ANG II on c-Fos and AT1-receptor expression in the rat brain

2001 ◽  
Vol 280 (4) ◽  
pp. R1095-R1104 ◽  
Author(s):  
Eva Moellenhoff ◽  
Annegret Blume ◽  
Juraj Culman ◽  
Bimal Chatterjee ◽  
Thomas Herdegen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Serum Response Factor ◽  
Receptor Expression ◽  
Transcriptional Level ◽  
Ang Ii ◽  
Element Binding Protein ◽  
Intracerebroventricular Injections ◽  
Receptor Number ◽  
Activating Transcription Factor

ANG II has been implicated in neuroplastic processes via stimulation of inducible transcription factors (ITF) in the brain. In the present study, we investigated the effects of acute vs. repetitive once daily intracerebroventricular injections of ANG II for 7 days on the expression of ITF and constitutive transcription factor (CTF) and the AT1 receptor in the median preoptic area (MnPO), the subfornical organ (SFO), and the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON). After repetitive injections, the expression of c-Fos declined by ∼50% in MnPO, SFO, PVN, and SON compared with controls injected once. The desensitization of c-Fos occurred on the transcriptional level as shown in the SON by RT-PCR. Apart from a novel expression of c-Jun in the SON, the ITF c-Jun, JunB, JunD, and Krox-24 did not change after repetitive stimulation. Neither were the CTF, calcium response element binding protein, activating transcription factor 2, and serum response factor altered after repetitive vs. single injections of ANG II. The AT1 receptor was coexpressed with c-Fos/c-Jun. Immunohistochemical stainings suggest an increase in AT1-receptor number in MnPO, SFO, PVN, and SON on chronic stimulation compared with once-injected controls. These findings demonstrate that repetitive periventricular stimulation with ANG II essentially alters the expression of transcription factors compared with acute stimulation and suggest c-Fos and c-Jun as major intermediates of the AT1-receptor transcription.

scholarly journals The NAC-like transcription factor CsNAC7 positively regulates the caffeine biosynthesis-related gene yhNMT1 in Camellia sinensis

2022 ◽  
Vol 9 ◽  
Author(s):  
Wenhui Ma ◽  
Xin Kang ◽  
Ping Liu ◽  
Kexin She ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Tea Plant ◽  
Transcriptional Level ◽  
Related Gene ◽  
Caffeine Synthase ◽  
N Terminus ◽  
Caffeine Biosynthesis ◽  
Encoding Gene

Abstract Caffeine is an important functional substance and is abundant in tea plant, but little is known about how its biosynthesis is regulated by transcription factors. In this study, the NAC-like transcription factor-encoding gene CsNAC7, which is involved in caffeine synthesis, was isolated from a Yinghong 9 cDNA library using a yeast one-hybrid assay; this gene comprises 1371 bp nucleotides and is predicted to encode 456 amino acids. The expression of CsNAC7 at the transcriptional level in tea shoots shared a similar pattern with that of the caffeine synthase gene yhNMT1 in the spring and summer, and its expressed protein was localized in the nucleus. Assays of gene activity showed that CsNAC7 has self-activation activity in yeast, that the active region is at the N-terminus, and that the transient expression of CsNAC7 could significantly promote the expression of yhNMT1 in tobacco leaves. In addition, overexpression or silencing of CsNAC7 significantly increased or decreased the expression of yhNMT1 and the accumulation of caffeine in transgenic tea calli, respectively. Our data suggest that the isolated transcription factor CsNAC7 positively regulates the caffeine synthase gene yhNMT1 and promotes caffeine accumulation in tea plant.

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