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 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.

scholarly journals Genome expression dynamics reveals parasitism regulatory landscape of the root-knot nematode Meloidogyne incognita and a promoter motif associated with effector genes

2021 ◽  
Author(s):  
Martine Da Rocha ◽  
Caroline Bournaud ◽  
Julie Dazeniere ◽  
Peter Thorpe ◽  
Clement Pellegrin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Meloidogyne Incognita ◽  
Life Stage ◽  
Regulation Of Gene Expression ◽  
Root Knot Nematode ◽  
Root Knot Nematodes ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Effector Genes ◽  
Spatio Temporal

Root-knot nematodes are the major contributor to the crop losses caused by nematodes. Root-knot nematodes secrete effectors into the plant, derived from two sets of pharyngeal gland cells, to manipulate host physiology and immunity. Successful completion of the life cycle, involving successive molts from egg to adult, covers morphologically and functionally distinct stages and will require precise control of gene expression, including effectors. The details of how root-knot nematodes regulate transcription remain sparse. Here, we report a life stage-specific transcriptome of Meloidogyne incognita. Combined with an available annotated genome, we explore the spatio-temporal regulation of gene expression. We reveal gene expression clusters and predicted functions that accompany the major developmental transitions. Focusing on effectors, we identify a putative cis-regulatory motif associated with expression in the dorsal glands: providing an insight into effector regulation. We combine the presence of this motif with several other criteria to predict a novel set of putative dorsal gland effectors. Finally, we show this motif, and thereby its utility, is broadly conserved across the Meloidogyne genus and termed it Mel-DOG. Taken together, we provide the first genome-wide analysis of spatio-temporal gene expression in a root-knot nematode, and identify a new set of candidate effector genes that will guide future functional analyses.

scholarly journals Removal of H3K27me3 by JMJ Proteins Controls Plant Development and Environmental Responses in Arabidopsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Nobutoshi Yamaguchi
Keyword(s):  
Gene Expression ◽  
Plant Development ◽  
Transcriptional Repression ◽  
Target Genes ◽  
Regulation Of Gene Expression ◽  
Histone H3 ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Repressive Histone Modification ◽  
Environmental Responses

Trimethylation of histone H3 lysine 27 (H3K27me3) is a highly conserved repressive histone modification that signifies transcriptional repression in plants and animals. In Arabidopsis thaliana, the demethylation of H3K27 is regulated by a group of JUMONJI DOMAIN-CONTANING PROTEIN (JMJ) genes. Transcription of JMJ genes is spatiotemporally regulated during plant development and in response to the environment. Once JMJ genes are transcribed, recruitment of JMJs to target genes, followed by demethylation of H3K27, is critically important for the precise control of gene expression. JMJs function synergistically and antagonistically with transcription factors and/or other epigenetic regulators on chromatin. This review summarizes the latest advances in our understanding of Arabidopsis H3K27me3 demethylases that provide robust and flexible epigenetic regulation of gene expression to direct appropriate development and environmental responses in plants.

scholarly journals Precise tuning of gene expression output levels in mammalian cells

2018 ◽  
Author(s):  
Yale S. Michaels ◽  
Mike B. Barnkob ◽  
Hector Barbosa ◽  
Toni A. Baeumler ◽  
Mary K. Thompson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Throughput Sequencing ◽  
Regulation Of Gene Expression ◽  
Antigen Expression ◽  
Control Of Gene Expression ◽  
Precise Control ◽  
Mouse Melanoma Model

ABSTRACTPrecise, analogue regulation of gene expression is critical for development, homeostasis and regeneration in mammals. In contrast, widely employed experimental and therapeutic approaches such as knock-in/out strategies are more suitable for binary control of gene activity, while RNA interference (RNAi) can lead to pervasive off-target effects and unpredictable levels of repression. Here we report on a method for the precise control of gene expression levels in mammalian cells based on engineered, synthetic microRNA response elements (MREs). To develop this system, we established a high-throughput sequencing approach for measuring the efficacy of thousands of miR-17 MRE variants. This allowed us to create a library of microRNA silencing-mediated fine-tuners (miSFITs) of varying strength that can be employed to control the expression of user specified genes. To demonstrate the value of this technology, we used a panel of miSFITs to tune the expression of a peptide antigen in a mouse melanoma model. This analysis revealed that antigen expression level is a key determinant of the anti-tumour immune response in vitro and in vivo. miSFITs are a powerful tool for modulating gene expression output levels with applications in research and cellular engineering.

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.

Control of gene expression and mitochondrial biogenesis in the muscular adaptation to endurance exercise

2006 ◽  
Vol 42 ◽  
pp. 13-29 ◽  
Author(s):  
Anna-Maria Joseph ◽  
Henriette Pilegaard ◽  
Anastassia Litvintsev ◽  
Lotte Leick ◽  
David A. Hood
Keyword(s):  
Gene Expression ◽  
Mitochondrial Biogenesis ◽  
Protein Import ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Mitochondrial Fission ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Control Of Gene Expression ◽  
Genes Encoding

Every time a bout of exercise is performed, a change in gene expression occurs within the contracting muscle. Over the course of many repeated bouts of exercise (i.e. training), the cumulative effects of these alterations lead to a change in muscle phenotype. One of the most prominent of these adaptations is an increase in mitochondrial content, which confers a greater resistance to muscle fatigue. This essay reviews current knowledge on the regulation of exercise-induced mitochondrial biogenesis at the molecular level. The major steps involved include, (i) transcriptional regulation of nuclear-encoded genes encoding mitochondrial proteins by the coactivator peroxisome-proliferator-activated receptor g coactivator-1, (ii) control of mitochondrial DNA gene expression by the transcription factor Tfam, (iii) mitochondrial fission and fusion mechanisms, and (iv) import of nuclear-derived gene products into the mitochondrion via the protein import machinery. It is now known that exercise can modify the rates of several of these steps, leading to mitochondrial biogenesis. An understanding of how exercise can produce this effect could help us decide whether exercise is beneficial for patients suffering from mitochondrial disorders, as well as a variety of metabolic diseases.

scholarly journals miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy

2020 ◽  
Vol 14 (12) ◽  
pp. e0008889
Author(s):  
Laurie Laugier ◽  
Ludmila Rodrigues Pinto Ferreira ◽  
Frederico Moraes Ferreira ◽  
Sandrine Cabantous ◽  
Amanda Farage Frade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Heart Tissue ◽  
Differentially Expressed ◽  
Biological Processes ◽  
Control Of Gene Expression ◽  
Network Analyses ◽  
Chronic Myocarditis

Chronic Chagas disease cardiomyopathy (CCC), an especially aggressive inflammatory dilated cardiomyopathy caused by lifelong infection with the protozoan Trypanosoma cruzi, is a major cause of cardiomyopathy in Latin America. Although chronic myocarditis may play a major pathogenetic role, little is known about the molecular mechanisms responsible for its severity. The aim of this study is to study the genes and microRNAs expression in tissues and their connections in regards to the pathobiological processes. To do so, we integrated for the first time global microRNA and mRNA expression profiling from myocardial tissue of CCC patients employing pathways and network analyses. We observed an enrichment in biological processes and pathways associated with the immune response and metabolism. IFNγ, TNF and NFkB were the top upstream regulators. The intersections between differentially expressed microRNAs and differentially expressed target mRNAs showed an enrichment in biological processes such as Inflammation, inflammation, Th1/IFN-γ-inducible genes, fibrosis, hypertrophy, and mitochondrial/oxidative stress/antioxidant response. MicroRNAs also played a role in the regulation of gene expression involved in the key cardiomyopathy-related processes fibrosis, hypertrophy, myocarditis and arrhythmia. Significantly, a discrete number of differentially expressed microRNAs targeted a high number of differentially expressed mRNAs (>20) in multiple processes. Our results suggest that miRNAs orchestrate expression of multiple genes in the major pathophysiological processes in CCC heart tissue. This may have a bearing on pathogenesis, biomarkers and therapy.

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 The Role of Translation Initiation Regulation in Haematopoiesis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Godfrey Grech ◽  
Marieke von Lindern
Keyword(s):  
Gene Expression ◽  
Translation Initiation ◽  
Translational Control ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Translation Control ◽  
Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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