scholarly journals An l-2-hydroxyglutarate biosensor based on specific transcriptional regulator LhgR

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhaoqi Kang ◽  
Manman Zhang ◽  
Kaiyu Gao ◽  
Wen Zhang ◽  
Wensi Meng ◽  
...  
Keyword(s):  
Biological Function ◽  
Transcriptional Regulator ◽  
Carbon Starvation ◽  
Gene Encoding ◽  
Starvation Response ◽  
Metabolism Regulation ◽  
Physiological Processes ◽  
Specific Effector ◽  
Genomic Neighborhood ◽  
Hg Accumulation

Abstractl-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation of l-2-HG metabolism remains poorly understood and none of regulator specifically responded to l-2-HG has been identified. Based on bacterial genomic neighborhood analysis of the gene encoding l-2-HG oxidase (LhgO), LhgR, which represses the transcription of lhgO in Pseudomonas putida W619, is identified in this study. LhgR is demonstrated to recognize l-2-HG as its specific effector molecule, and this allosteric transcription factor is then used as a biorecognition element to construct an l-2-HG-sensing FRET sensor. The l-2-HG sensor is able to conveniently monitor the concentrations of l-2-HG in various biological samples. In addition to bacterial l-2-HG generation during carbon starvation, biological function of the l-2-HG dehydrogenase and hypoxia induced l-2-HG accumulation are also revealed by using the l-2-HG sensor in human cells.

scholarly journals A fluorescent l-2-hydroxyglutarate biosensor

2020 ◽  
Author(s):  
Zhaoqi Kang ◽  
Manman Zhang ◽  
Kaiyu Gao ◽  
Wen Zhang ◽  
Yidong Liu ◽  
...  
Keyword(s):  
Carbon Starvation ◽  
Biological Functions ◽  
Gene Encoding ◽  
Starvation Response ◽  
Effector Molecule ◽  
Metabolism Regulation ◽  
Physiological Processes ◽  
Specific Effector ◽  
Genomic Neighborhood ◽  
Hg Accumulation

Abstractl-2-Hydroxyglutarate (l-2-HG) plays important roles in diverse physiological processes, such as carbon starvation response, tumorigenesis, and hypoxic adaptation. Despite its importance and intensively studied metabolism, regulation of l-2-HG metabolism remains poorly understood and a regulator specifically responded to l-2-HG has never been identified. Based on the genomic neighborhood analysis of the gene encoding l-2-HG oxidase (LhgO), LhgR, which represses the transcription of lhgO, was identified in Pseudomonas putida W619 in this study. LhgR was demonstrated to recognize l-2-HG as its specific effector molecule, and this allosteric transcription factor was then used as a biorecognition element for construction of l-2-HG-sensing FRET sensor. The newly developed l-2-HG sensor can conveniently monitor the concentrations of l-2-HG in various biological samples. In addition to bacterial l-2-HG generation during carbon starvation, biological functions of the l-2-HG dehydrogenase and hypoxia induced l-2-HG accumulation were also revealed by using the l-2-HG sensor in human cells.

scholarly journals Complex transcriptional regulation of the Saccharomyces cerevisiae CYB2 gene encoding cytochrome b2: CYP1(HAP1) activator binds to the CYB2 upstream activation site UAS1-B2.

1991 ◽  
Vol 11 (7) ◽  
pp. 3762-3772 ◽  
Author(s):  
T Lodi ◽  
B Guiard
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Regulatory Region ◽  
Transcriptional Regulator ◽  
Direct Analysis ◽  
Transcriptional Level ◽  
Glucose Fermentation ◽  
Gene Encoding ◽  
Dnase I Footprinting ◽  
Mrna Transcripts ◽  
Binding Sequence

Expression of the Saccharomyces cerevisiae gene encoding cytochrome b2 (EC 1.2.2.3), CYB2, was investigated by direct analysis of mRNA transcripts and by measurement of the expression of lacZ fused to the CYB2 control regions. These studies indicated that regulation of the CYB2 gene is subject to several metabolic controls at the transcriptional level: inhibition due to glucose fermentation, induction by lactate, and inhibition in anaerobiosis or in absence of heme biosynthesis. Furthermore, we have shown that the CYB2 promoter contains one cis negative regulatory region and two heme-dependent positive regions, one of which is controlled by the transcriptional regulator CYP1 (HAP1) which is involved in the modulation of the expression of several oxygen-regulated genes. The CYP1 (HAP1)-binding sequence was located by gel retardation and DNase I footprinting experiments and compared with the binding sequences previously characterized in detail (UAS1CYC1, UAS'CYP3 (CYC7), and UASCTT1).

scholarly journals A Conserved Carbon Starvation Response Underlies Bud Dormancy in Woody and Herbaceous Species

2017 ◽  
Vol 8 ◽  
Author(s):  
Carlos Tarancón ◽  
Eduardo González-Grandío ◽  
Juan C. Oliveros ◽  
Michael Nicolas ◽  
Pilar Cubas
Keyword(s):  
Carbon Starvation ◽  
Bud Dormancy ◽  
Herbaceous Species ◽  
Starvation Response

Reduction of a Kinetic Model of the Carbon Starvation Response in Escherichia coli

2009 ◽  
Vol 42 (10) ◽  
pp. 27-32
Author(s):  
Delphine Ropers ◽  
Valentina Baldazzi ◽  
Hidde de Jong
Keyword(s):  
Escherichia Coli ◽  
Kinetic Model ◽  
Carbon Starvation ◽  
Starvation Response

scholarly journals AMPK: a therapeutic target of heart failure—not only metabolism regulation

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xuan Li ◽  
Jia Liu ◽  
Qingguo Lu ◽  
Di Ren ◽  
Xiaodong Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Function ◽  
Critical Role ◽  
Ampk Activation ◽  
Atp Production ◽  
Metabolism Regulation ◽  
Physiological Processes ◽  
Clinical Drugs ◽  
Serious Disease ◽  
Amp Activated Protein Kinase

Abstract Heart failure (HF) is a serious disease with high mortality. The incidence of this disease has continued to increase over the past decade. All cardiovascular diseases causing dysfunction of various physiological processes can result in HF. AMP-activated protein kinase (AMPK), an energy sensor, has pleiotropic cardioprotective effects and plays a critical role in the progression of HF. In this review, we highlight that AMPK can not only improve the energy supply in the failing heart by promoting ATP production, but can also regulate several important physiological processes to restore heart function. In addition, we discuss some aspects of some potential clinical drugs which have effects on AMPK activation and may have value in treating HF. More studies, especially clinical trials, should be done to evaluate manipulation of AMPK activation as a potential means of treating HF.

scholarly journals Structure of the human TIMP-3 gene and its cell cycle-regulated promoter

1995 ◽  
Vol 311 (2) ◽  
pp. 549-554 ◽  
Author(s):  
M Wick ◽  
R Härönen ◽  
D Mumberg ◽  
C Bürger ◽  
B R Olsen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Alternative Polyadenylation ◽  
Regulatory Elements ◽  
Detailed Knowledge ◽  
Gene Encoding ◽  
Cycle Progression ◽  
Physiological Processes ◽  
Cycle Regulation

The gene encoding tissue inhibitor of metalloproteinases-3 (TIMP-3) is regulated during development, mitogenic stimulation and normal cell cycle progression. The TIMP-3 gene is structurally altered or deregulated in certain diseases of the eye and in tumour cells. A detailed knowledge of the TIMP-3 gene and its regulatory elements is therefore of paramount importance to understand its role in development, cell cycle progression and disease. In this study, we present the complete structure of the human TIMP-3 gene. We show that TIMP-3 is a TATA-less gene, which initiates transcription at one major site, is composed of five exons and four introns spanning a region of approximately 30 kb, and gives rise to three distinct mRNAs, presumably due to the usage of alternative polyadenylation signals. Using somatic cell hybrids the TIMP-3 locus was mapped to chromosomal location 22q13.1 We also show that the TIMP-3 5′ flanking region is sufficient to confer both high basal level expression in growing cells and cell cycle regulation in serum-stimulated cells. While the first 112 bases of the promoter, which harbour multiple Sp1 sites, were found to suffice for high basal level activity, the adjacent region spanning positions -463 and -112 was found to be a major determinant of serum inducibility. These results provide an important basis for further investigations addressing the role of TIMP-3 in physiological processes and pathological conditions.

Qualitative simulation of the carbon starvation response in Escherichia coli

Biosystems ◽  
2006 ◽  
Vol 84 (2) ◽  
pp. 124-152 ◽  
Author(s):  
Delphine Ropers ◽  
Hidde de Jong ◽  
Michel Page ◽  
Dominique Schneider ◽  
Johannes Geiselmann
Keyword(s):  
Escherichia Coli ◽  
Carbon Starvation ◽  
Starvation Response ◽  
Qualitative Simulation

scholarly journals The gene encoding the transcriptional regulator Yin Yang 1 (YY1) is a myeloid transforming gene interfering with neutrophilic differentiation

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 1111-1117 ◽  
Author(s):  
Stefan J. Erkeland ◽  
Marijke Valkhof ◽  
Claudia Heijmans-Antonissen ◽  
Ruud Delwel ◽  
Peter J. M. Valk ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Transcriptional Start Site ◽  
Leukemia Virus ◽  
Transcriptional Regulator ◽  
Luciferase Reporter ◽  
Insertion Mutagenesis ◽  
Gene Encoding ◽  
Protein Levels ◽  
Yin Yang 1 ◽  
Yin Yang

AbstractThe genetic defects underlying the pathogenesis of acute myeloid leukemia (AML) are still largely unknown. Retroviral insertion mutagenesis in mice has become a powerful tool to identify candidate genes involved in the development of leukemia and lymphoma. We have used this strategy with the 1.4 strain of Graffi murine leukemia virus (MuLV), which predominantly causes myeloid leukemias. Here, we report that Graffi-1.4–induced AML frequently harbors virus integrations in the gene encoding the transcription factor Yin Yang 1 (YY1). These integrations occurred in both orientations, and all were located in the 5′ promoter region of the gene, 0.5 to 1.5 kb upstream of the major transcriptional start site. Luciferase reporter assays showed that virus integration in this region increases promoter activity and renders it independent of a functional binding site for Sp1, a major transcriptional regulator of YY1. We used the murine 32D model to study the consequence of perturbed YY1 expression for myelopoiesis. YY1 protein levels were high in 32D parental cells maintained in interleukin-3–containing medium, but they dropped when the cells were induced to differentiate by granulocyte–colony-stimulating factor (G-CSF). Strikingly, G-CSF–induced neutrophilic differentiation was reduced in 32D cell transfectants ectopically expressing YY1. In similar experiments on primary bone marrow cells, enforced YY1 expression blocked the outgrowth of CFU-GM colonies. Increased YY1 expression was seen in some cases of human AML. Collectively, these data imply a possible role of perturbed expression of YY1 in the development of AML through interference with the myeloid differentiation program in the leukemic progenitor cells.

scholarly journals Cloning and characterization of btr, a Bordetella pertussis gene encoding an FNR-like transcriptional regulator.

1993 ◽  
Vol 175 (22) ◽  
pp. 7228-7235 ◽  
Author(s):  
J D Bannan ◽  
M J Moran ◽  
J I MacInnes ◽  
G A Soltes ◽  
R L Friedman
Keyword(s):  
Bordetella Pertussis ◽  
Transcriptional Regulator ◽  
Gene Encoding

scholarly journals NtcA is responsible for accumulation of the small isoform of ferredoxin:NADP oxidoreductase

Microbiology ◽  
2014 ◽  
Vol 160 (4) ◽  
pp. 789-794 ◽  
Author(s):  
Amin Omairi-Nasser ◽  
Carla V. Galmozzi ◽  
Amel Latifi ◽  
M. Isabel Muro-Pastor ◽  
Ghada Ajlani
Keyword(s):  
Binding Site ◽  
Translation Initiation ◽  
Transcriptional Regulator ◽  
Growth Conditions ◽  
Gene Encoding

In several cyanobacteria, petH, the gene encoding ferredoxin:NADP oxidoreductase (FNR), is transcribed from at least two promoters depending on growth conditions. Two transcripts (short and long) are translated from two different translation initiation sites, resulting in two isoforms (large and small, respectively). Here, we show that in Synechocystis PCC6803 the global transcriptional regulator NtcA activates transcription from the distal petH promoter. Modification of the NtcA-binding site prevents NtcA binding to the promoter in vitro and abolishes accumulation of the small isoform of FNR in vivo. We also demonstrate that a similar petH transcription and translation regime occurs in other cyanobacteria. The conditions under which this system operates provide hints for the function of each FNR isoform.

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