scholarly journals Amino acid limitation regulates gene expression

1999 ◽  
Vol 58 (3) ◽  
pp. 625-632 ◽  
Author(s):  
Alain Bruhat ◽  
Céline Jousse ◽  
Pierre Fafournoux
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Essential Amino Acids ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Control Of Gene Expression

In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0·0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.

Amino acid regulation of gene expression

2000 ◽  
Vol 351 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Pierre FAFOURNOUX ◽  
Alain BRUHAT ◽  
Céline JOUSSE
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Asparagine Synthetase ◽  
Present Review ◽  
Mrna Levels ◽  
Control Of Gene Expression ◽  
Amino Acid Availability

The impact of nutrients on gene expression in mammals has become an important area of research. Nevertheless, the current understanding of the amino acid-dependent control of gene expression is limited. Because amino acids have multiple and important functions, their homoeostasis has to be finely maintained. However, amino-acidaemia can be affected by certain nutritional conditions or various forms of stress. It follows that mammals have to adjust several of their physiological functions involved in the adaptation to amino acid availability by regulating the expression of numerous genes. The aim of the present review is to examine the role of amino acids in regulating mammalian gene expression and protein turnover. It has been reported that some genes involved in the control of growth or amino acid metabolism are regulated by amino acid availability. For instance, limitation of several amino acids greatly increases the expression of the genes encoding insulin-like growth factor binding protein-1, CHOP (C/EBP homologous protein, where C/EBP is CCAAT/enhancer binding protein) and asparagine synthetase. Elevated mRNA levels result from both an increase in the rate of transcription and an increase in mRNA stability. Several observations suggest that the amino acid regulation of gene expression observed in mammalian cells and the general control process described in yeast share common features. Moreover, amino acid response elements have been characterized in the promoters of the CHOP and asparagine synthetase genes. Taken together, the results discussed in the present review demonstrate that amino acids, by themselves, can, in concert with hormones, play an important role in the control of gene expression.

scholarly journals Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity

2019 ◽  
Vol 20 (6) ◽  
pp. 1386 ◽  
Author(s):  
Diego Haro ◽  
Pedro Marrero ◽  
Joana Relat
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Regulation Of Gene Expression ◽  
Peroxisome Proliferator ◽  
Nutritional Regulation ◽  
Control Of Gene Expression ◽  
Nutritional Interventions ◽  
Precise Control

The ability to detect changes in nutrient levels and generate an adequate response to these changes is essential for the proper functioning of living organisms. Adaptation to the high degree of variability in nutrient intake requires precise control of metabolic pathways. Mammals have developed different mechanisms to detect the abundance of nutrients such as sugars, lipids and amino acids and provide an integrated response. These mechanisms include the control of gene expression (from transcription to translation). This review reports the main molecular mechanisms that connect nutrients’ levels, gene expression and metabolism in health. The manuscript is focused on sugars’ signaling through the carbohydrate-responsive element binding protein (ChREBP), the role of peroxisome proliferator-activated receptors (PPARs) in the response to fat and GCN2/activating transcription factor 4 (ATF4) and mTORC1 pathways that sense amino acid concentrations. Frequently, alterations in these pathways underlie the onset of several metabolic pathologies such as obesity, insulin resistance, type 2 diabetes, cardiovascular diseases or cancer. In this context, the complete understanding of these mechanisms may improve our knowledge of metabolic diseases and may offer new therapeutic approaches based on nutritional interventions and individual genetic makeup.

scholarly journals Pit-1β reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner

2005 ◽  
Vol 185 (1) ◽  
pp. 173-185 ◽  
Author(s):  
A L Ferry ◽  
D M Locasto ◽  
L B Meszaros ◽  
J C Bailey ◽  
M D Jonsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Anterior Pituitary ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Pituitary Hormone ◽  
Dependent Manner ◽  
Creb Binding Protein ◽  
Control Of Gene Expression ◽  
Protein Recruitment

Many transcription factors are expressed as multiple isoforms with distinct effects on the regulation of gene expression, and the functional consequences of structural differences between transcription factor isoforms may allow for precise control of gene expression. The pituitary transcription factor isoforms Pit-1 and Pit-1β differentially regulate anterior pituitary hormone gene expression. Pit-1 is required for the development of and appropriate hormone expression by anterior pituitary somatotrophs and lactotrophs. Pit-1β differs structurally from Pit-1 by the splice-insertion of the 26-residue β-domain in the trans-activation domain, and it differs functionally from Pit-1 in that it represses expression of the prolactin promoter in a cell-type specific manner. In order to identify signal and promoter context requirements for repression by Pit-1β, we examined its function in the presence of physiological regulatory signals as well as wild-type and mutant Pit-1-dependent target promoters. Here, we demonstrate that Pit-1β impairs recruitment of cAMP response element-binding protein (CREB)-binding protein to the promoters that it represses. In addition, we show that repression of target promoter activity, reduction in promoter histone acetylation, and decrease of CREB-binding protein recruitment all depend on promoter context. These findings provide a mechanism for promoter-specific repression by Pit-1β.

scholarly journals Gene expression of the three members of hepatocyte nuclear factor-3 is differentially regulated by nutritional and hormonal factors

2000 ◽  
Vol 167 (1) ◽  
pp. R1-R5 ◽  
Author(s):  
M Imae ◽  
Y Inoue ◽  
Z Fu ◽  
H Kato ◽  
T Noguchi
Keyword(s):  
Gene Expression ◽  
Mrna Level ◽  
Regulation Of Gene Expression ◽  
Diabetic Rats ◽  
Physiological Status ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Protein Free Diet

Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.

scholarly journals Generally applicable transcriptome-wide analysis of translational efficiency using anota2seq

2017 ◽  
Author(s):  
Christian Oertlin ◽  
Julie Lorent ◽  
Valentina Gandin ◽  
Carl Murie ◽  
Laia Masvidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Analytical Methods ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Ribosome Profiling ◽  
Translation Regulation ◽  
Translational Efficiency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Mtor Inhibition

ABSTRACTmRNA translation plays an evolutionarily conserved role in homeostasis and when dysregulated results in various disorders. Optimal and universally applicable analytical methods to study transcriptome-wide changes in translational efficiency are therefore critical for understanding the complex role of translation regulation under physiological and pathological conditions. Techniques used to interrogate translatomes, including polysome- and ribosome-profiling, require adjustment for changes in total mRNA levels to capture bona fide alterations in translational efficiency. Herein, we present the anota2seq algorithm for such analysis using data from ribosome- or polysome-profiling quantified by DNA-microarrays or RNA sequencing, which outperforms current methods for identification of changes in translational efficiency. In contrast to available analytical methods, anota2seq also allows capture of an underappreciated mode for regulation of gene expression whereby translation acts as a buffering mechanism which maintains constant protein levels despite fluctuations in mRNA levels (“translational buffering”). Application of anota2seq shows that insulin affects gene expression at multiple levels, in a largely mTOR-dependent manner. Moreover, insulin induces levels of a subset of mRNAs independently of mTOR that undergo translational buffering upon mTOR inhibition. Thus, the universal anota2seq algorithm allows efficient and hitherto unprecedented interrogation of translatomes and enables studies of translational buffering which represents an unexplored mechanism for regulating of gene expression.

scholarly journals Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism

2007 ◽  
Vol 293 (1) ◽  
pp. E165-E171 ◽  
Author(s):  
Christopher D. Morrison ◽  
Xiaochun Xi ◽  
Christy L. White ◽  
Jianping Ye ◽  
Roy J. Martin
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Amino Acid ◽  
Food Intake ◽  
Mtor Signaling ◽  
Acid Mixture ◽  
Mrna Levels ◽  
Amino Acid Availability ◽  
The Brain ◽  
Amino Acid Concentrations

Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake ( P < 0.05) and hypothalamic Agouti-related protein ( Agrp) gene expression ( P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 μg) suppressed 24-h food intake ( P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1–7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1–7 cells ( P < 0.01), and this effect was attenuated by replacement of the amino acid leucine ( P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1–7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids ( P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.

scholarly journals Amino Acids Control Mammalian Gene Transcription: Activating Transcription Factor 2 Is Essential for the Amino Acid Responsiveness of the CHOP Promoter

2000 ◽  
Vol 20 (19) ◽  
pp. 7192-7204 ◽  
Author(s):  
Alain Bruhat ◽  
Céline Jousse ◽  
Valérie Carraro ◽  
Andreas M. Reimold ◽  
Marc Ferrara ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acids ◽  
Transcription Factor ◽  
Amino Acid ◽  
Transcriptional Activation ◽  
Dominant Negative Mutant ◽  
Transient Expression Assay ◽  
Control Of Gene Expression ◽  
Mammalian Gene ◽  
Activating Transcription Factor

ABSTRACT In mammals, plasma concentration of amino acids is affected by nutritional or pathological conditions. It has been well established that nutrients, and particularly amino acids, are involved in the control of gene expression. Here we examined the molecular mechanisms involved in the regulation ofCHOP (a CCAAT/enhancer-binding protein [C/EBP]-related gene) expression upon amino acid limitation. We have previously shown that regulation of CHOP mRNA expression by amino acid concentration has both transcriptional and posttranscriptional components. We report the analysis ofcis- and trans-acting elements involved in the transcriptional activation of the human CHOPgene by leucine starvation. Using a transient expression assay, we show that a cis-positive element is essential for amino acid regulation of the CHOP promoter. This sequence is the first described that can regulate a basal promoter in response to starvation for several individual amino acids and therefore can be called an amino acid response element (AARE). In addition, we show that the CHOP AARE is related to C/EBP and ATF/CRE binding sites and binds in vitro the activating transcription factor 2 (ATF-2) in starved and unstarved conditions. Using ATF-2-deficient mouse embryonic fibroblasts and an ATF-2-dominant negative mutant, we demonstrate that expression of this transcription factor is essential for the transcriptional activation of CHOP by leucine starvation. Altogether, these results suggest that ATF-2 may be a member of a cascade of molecular events by which the cellular concentration of amino acids can regulate mammalian gene expression.

DDX21 interacts with nuclear AGO2 and regulates the alternative splicing of SMN2

2020 ◽  
Vol 85 (2) ◽  
pp. 272-279
Author(s):  
Mengting Gong ◽  
Xi Zhang ◽  
Yaru Wang ◽  
Guiyan Mao ◽  
Yangqi Ou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Gene Silencing ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Dependent Manner ◽  
Indirect Interaction ◽  
Multiple Gene ◽  
Multiple Gene Silencing

ABSTRACT AGO2 is the only member of mammalian Ago protein family that possesses the catalytic activity and plays a central role in gene silencing. Recently researches reported that multiple gene silencing factors, including AGO2, function in the nuclei. The molecular mechanisms of the gene silencing factors functioning in nuclei are conducive to comprehend the roles of gene silencing in pretranslational regulation of gene expression. Here, we report that AGO2 interacts with DDX21 indirectly in an RNA-dependent manner by Co-IP and GST-Pulldown assays and the 2 proteins present nuclei foci in the immunofluorescence experiments. We found that DDX21 up-regulated the protein level of AGO2 and participated in target gene, SNM2, alternative splicing involved in AGO2 by the indirect interaction with AGO2, which produced different transcripts of SMN2 in discrepant expression level. This study laid important experiment foundation for the further analysis of the nuclear functions of gene silencing components.

scholarly journals NMDAR-mediated transcriptional control of gene expression in the specification of interneuron subtype identity

2020 ◽  
Author(s):  
Vivek Mahadevan ◽  
Apratim Mitra ◽  
Yajun Zhang ◽  
Areg Peltekian ◽  
Ramesh Chittajallu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Medial Ganglionic Eminence ◽  
Membrane Excitability ◽  
Control Of Gene Expression ◽  
Road Map ◽  
Physiological Properties ◽  
Nmdar Subunit

AbstractMedial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates subtype-specific transcriptional regulation of gene expression in MGE-derived interneurons, leading to altered subtype identities. Notably, MGE-specific conditional Grin1 loss results in a systemic downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders, particularly schizophrenia. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.

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