scholarly journals Unconventional metabolites in chromatin regulation

2022 ◽  
Author(s):  
Liubov Gapa ◽  
Huda Alfardus ◽  
Wolfgang Fischle
Keyword(s):  
Amino Acids ◽  
Functional State ◽  
Molecular Level ◽  
Chromatin State ◽  
Chromatin Modifications ◽  
Chromatin Regulation ◽  
Phenotypic Changes ◽  
Intermediate Metabolism ◽  
Adenosyl Methionine ◽  
Cellular Pathways

Chromatin, the complex of DNA and histone proteins, serves as a main integrator of cellular signals. Increasing evidence links cellular functional to chromatin state. Indeed, different metabolites are emerging as modulators of chromatin function and structure. Alterations in chromatin state are decisive for regulating all aspects of genome function and ultimately have the potential to produce phenotypic changes. Several metabolites such as acetyl-CoA, S-adenosyl methionine (SAM) or adenosine triphosphate (ATP) have now been well characterized as main substrates or cofactors of chromatin modifying enzymes. However, there are other metabolites that can directly interact with chromatin influencing its state or that modulate the properties of chromatin regulatory factors. Also, there is a growing list of atypical enzymatic and non-enzymatic chromatin modifications that originate from different cellular pathways that have not been in the limelight of chromatin research. Here, we summarize different properties and functions of uncommon regulatory molecules originating from intermediate metabolism of lipids, carbohydrates and amino acids. Based on the various modes of action on chromatin and the plethora of putative, so far not described chromatin regulating metabolites, we propose that there are more links between cellular functional state and chromatin regulation to be discovered. We hypothesize that these connections could provide interesting starting points for interfering with cellular epigenetic states at a molecular level.

Structural and Functional State of Erythrocyte Membranes at Drug Addiction

2021 ◽  
Vol 18 (1) ◽  
pp. 13-19
Author(s):  
A.I. Rabadanova ◽  
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Functional State ◽  
Conformational Changes ◽  
Structural Integrity ◽  
Fluorescence Analysis ◽  
Heroin Addiction ◽  
Dimensional Structure ◽  
Erythrocyte Membranes ◽  
Drug Addicts

The steady growth in the number of drug addicts, especially among young people, dictates the need to find ways to prevent and treat this disease. In this regard, there is a need for a more detailed study of the mechanisms of the course of this disease using modern research methods, such as atomic force microscopy and fluorescence analysis of amino acid residues. Purpose of the work: to reveal the structural and functional state of erythrocyte membranes in drug addiction. Materials and methods. The studies were carried out on the erythrocyte membranes of 60 subjects suffering from heroin addiction. The shape and topography of the erythrocyte surface were studied, and spectral analysis of the proteins of the erythrocyte membranes was carried out. Results. The conducted AFM studies of erythrocyte membranes indicate the heterogeneity of the surface mechanical properties of the erythrocyte membranes of drug addicts. The data obtained indicate an acceleration of the aging process of erythrocytes in drug addiction, which goes in two ways: the formation of outgrowths on the plasmolemma, which subsequently die off (echinocytes) and invagination of the plasmolemma of erythrocytes (spherocytes). The fluorescence spectrum of amino acids in erythrocytes of drug addicts is characterized by a significant decrease in the intensity of almost all peaks and a shift of the fluorescence peak to the short-wave region. Findings. With drug addiction, changes in the structural integrity of red blood cells are noted. In people with drug addiction, in comparison with healthy people, there is a higher variability of the morphology of erythrocytes, which is expressed in a significant increase in the proportion of echinocytes and spherocytes against the background of a significant decrease in the number of discocytes. For the membrane proteins of erythrocytes of drug addicts, conformational changes are characteristic, manifested in a decrease in the intensity of fluorescence of aromatic amino acids, which indicates their structural modification and significant vulnerability of the hematopoietic system. They are largely determined by changes in the fluorescence intensity of tryptophan and, to a lesser extent, tyrosine, which indicates the preservation of the three-dimensional structure of the protein.

scholarly journals Live-Cell Imaging Probes to Track Chromatin Modification Dynamics

Microscopy ◽  
2021 ◽  
Author(s):  
Yuko Sato ◽  
Masaru Nakao ◽  
Hiroshi Kimura
Keyword(s):  
Fluorescent Dyes ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Chromatin Modification ◽  
Resonance Energy ◽  
Cell Types ◽  
Live Cell ◽  
Chromatin Modifications ◽  
Chromatin Regulation ◽  
Single Chain

Abstract The spatiotemporal organization of chromatin is regulated at different levels in the nucleus. Epigenetic modifications such as DNA methylation and histone modifications are involved in chromatin regulation and play fundamental roles in genome function. While the one-dimensional epigenomic landscape in many cell types has been revealed by chromatin immunoprecipitation and sequencing, the dynamic changes of chromatin modifications and their relevance to chromatin organization and genome function remain elusive. Live-cell probes to visualize chromatin and its modifications have become powerful tools to monitor dynamic chromatin regulation. Bulk chromatin can be visualized both by small fluorescent dyes and fluorescent proteins, and specific endogenous genomic loci have been detected by adapting genome-editing tools. To track chromatin modifications in living cells, various types of probes have been developed. Protein domains that bind to specific modifications weakly, such as chromodomains for histone methylation, can be repeated to create a tighter binding probe that can then be tagged with a fluorescent protein. It has also been demonstrated that antigen-binding fragments and single-chain variable fragments from modification-specific antibodies can serve as binding probes without disturbing cell division, development and, differentiation. These modification-binding modules are used in modification sensors based on fluorescence/Förster resonance energy transfer to measure the intramolecular conformation changes triggered by modifications. Other probes can be created using a bivalent binding system, such as fluorescence complementation, or luciferase chemiluminescence. Live-cell chromatin modification imaging using these probes will address dynamic chromatin regulation and will be useful for assaying and screening effective epigenome drugs in cells and organisms.

scholarly journals Metabolic Signaling into Chromatin Modifications in the Regulation of Gene Expression

2018 ◽  
Vol 19 (12) ◽  
pp. 4108 ◽  
Author(s):  
Tian Gao ◽  
Zyanya Díaz-Hirashi ◽  
Francisco Verdeguer
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Disorders ◽  
Regulation Of Gene Expression ◽  
Hormonal Control ◽  
The Other ◽  
Specific Gene ◽  
Chromatin Modifications ◽  
Metabolic Signaling ◽  
Adenosyl Methionine ◽  
Chromatin Acetylation

The regulation of cellular metabolism is coordinated through a tissue cross-talk by hormonal control. This leads to the establishment of specific transcriptional gene programs which adapt to environmental stimuli. On the other hand, recent advances suggest that metabolic pathways could directly signal into chromatin modifications and impact on specific gene programs. The key metabolites acetyl-CoA or S-adenosyl-methionine (SAM) are examples of important metabolic hubs which play in addition a role in chromatin acetylation and methylation. In this review, we will discuss how intermediary metabolism impacts on transcription regulation and the epigenome with a particular focus in metabolic disorders.

scholarly journals How much of protein sequence space has been explored by life on Earth?

2008 ◽  
Vol 5 (25) ◽  
pp. 953-956 ◽  
Author(s):  
David T.F Dryden ◽  
Andrew R Thomson ◽  
John H White
Keyword(s):  
Amino Acids ◽  
Genome Size ◽  
Sequence Space ◽  
Protein Sequence ◽  
Molecular Level ◽  
Functional Protein ◽  
The Earth ◽  
Life On Earth ◽  
Protein Sequence Space ◽  
Lower Limits

We suggest that the vastness of protein sequence space is actually completely explorable during the populating of the Earth by life by considering upper and lower limits for the number of organisms, genome size, mutation rate and the number of functionally distinct classes of amino acids. We conclude that rather than life having explored only an infinitesimally small part of sequence space in the last 4 Gyr, it is instead quite plausible for all of functional protein sequence space to have been explored and that furthermore, at the molecular level, there is no role for contingency.

scholarly journals Photochemistry and photophysics of mycosporine-like amino acids and gadusols, nature’s ultraviolet screens

2015 ◽  
Vol 87 (9-10) ◽  
pp. 979-996 ◽  
Author(s):  
Raul Losantos ◽  
Diego Sampedro ◽  
María Sandra Churio
Keyword(s):  
Amino Acids ◽  
Rational Design ◽  
Molecular Level ◽  
Light Stimulus ◽  
Theoretical Studies ◽  
Chemical Systems ◽  
Experimental And Theoretical Studies

AbstractMycosporine-like amino acids (MAAs) and related gadusols are among the most prominent examples of metabolites suggested to act as UV-sunscreens. This review illustrates how experimental and theoretical studies on model MAAs and gadusol offer a helpful description of the photoprotective mechanism at the molecular level. This knowledge may contribute to the rational design of chemical systems with predictable and tuneable response to light stimulus. Synthetic efforts to obtain MAAs and simplified related structures are also discussed.

scholarly journals Protein Oxidative Damage at the Crossroads of Cellular Senescence, Aging, and Age-Related Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Martin A. Baraibar ◽  
Liang Liu ◽  
Emad K. Ahmed ◽  
Bertrand Friguet
Keyword(s):  
Lipid Peroxidation ◽  
Protein Modification ◽  
Replicative Senescence ◽  
Human Fibroblasts ◽  
Potential Effect ◽  
Senescent Phenotype ◽  
Intermediate Metabolism ◽  
Age Related ◽  
Cellular Pathways

Protein damage mediated by oxidation, protein adducts formation with advanced glycated end products and with products of lipid peroxidation, has been implicated during aging and age-related diseases, such as neurodegenerative diseases. Increased protein modification has also been described upon replicative senescence of human fibroblasts, a valid model for studying agingin vitro. However, the mechanisms by which these modified proteins could impact on the development of the senescent phenotype and the pathogenesis of age-related diseases remain elusive. In this study, we performedin silicoapproaches to evidence molecular actors and cellular pathways affected by these damaged proteins. A database of proteins modified by carbonylation, glycation, and lipid peroxidation products during aging and age-related diseases was built and compared to those proteins identified during cellular replicative senescencein vitro. Common cellular pathways evidenced by enzymes involved in intermediate metabolism were found to be targeted by these modifications, although different tissues have been examined. These results underscore the potential effect of protein modification in the impairment of cellular metabolism during aging and age-related diseases.

scholarly journals Multiple inputs control sulfur-containing amino acid synthesis inSaccharomyces cerevisiae

2014 ◽  
Vol 25 (10) ◽  
pp. 1653-1665 ◽  
Author(s):  
Meru J. Sadhu ◽  
James J. Moresco ◽  
Anjali D. Zimmer ◽  
John R. Yates ◽  
Jasper Rine
Keyword(s):  
Amino Acids ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Acid Synthesis ◽  
Phospholipid Synthesis ◽  
Amino Acid Synthesis ◽  
Sam Synthetase ◽  
Cysteine Synthesis ◽  
Adenosyl Methionine ◽  
Sulfur Containing

In Saccharomyces cerevisiae, transcription of the MET regulon, which encodes the proteins involved in the synthesis of the sulfur-containing amino acids methionine and cysteine, is repressed by the presence of either methionine or cysteine in the environment. This repression is accomplished by ubiquitination of the transcription factor Met4, which is carried out by the SCF(Met30) E3 ubiquitin ligase. Mutants defective in MET regulon repression reveal that loss of Cho2, which is required for the methylation of phosphatidylethanolamine to produce phosphatidylcholine, leads to induction of the MET regulon. This induction is due to reduced cysteine synthesis caused by the Cho2 defects, uncovering an important link between phospholipid synthesis and cysteine synthesis. Antimorphic mutants in S-adenosyl-methionine (SAM) synthetase genes also induce the MET regulon. This effect is due, at least in part, to SAM deficiency controlling the MET regulon independently of SAM's contribution to cysteine synthesis. Finally, the Met30 protein is found in two distinct forms whose relative abundance is controlled by the availability of sulfur-containing amino acids. This modification could be involved in the nutritional control of SCF(Met30) activity toward Met4.

scholarly journals Chromatin regulation of somatic abiotic stress memory

2020 ◽  
Vol 71 (17) ◽  
pp. 5269-5279 ◽  
Author(s):  
Isabel Bäurle ◽  
Inês Trindade
Keyword(s):  
Abiotic Stress ◽  
Molecular Level ◽  
Recovery Phase ◽  
Chromatin Regulation ◽  
Priming Effects ◽  
Stress Memory ◽  
Recent Developments ◽  
Single Stress ◽  
Different Levels ◽  
Plant Abiotic Stress

Abstract In nature, plants are often subjected to periods of recurrent environmental stress that can strongly affect their development and productivity. To cope with these conditions, plants can remember a previous stress, which allows them to respond more efficiently to a subsequent stress, a phenomenon known as priming. This ability can be maintained at the somatic level for a few days or weeks after the stress is perceived, suggesting that plants can store information of a past stress during this recovery phase. While the immediate responses to a single stress event have been extensively studied, knowledge on priming effects and how stress memory is stored is still scarce. At the molecular level, memory of a past condition often involves changes in chromatin structure and organization, which may be maintained independently from transcription. In this review, we will summarize the most recent developments in the field and discuss how different levels of chromatin regulation contribute to priming and plant abiotic stress memory.

scholarly journals Fermentative N-Methylanthranilate Production by Engineered Corynebacterium glutamicum

2020 ◽  
Vol 8 (6) ◽  
pp. 866 ◽  
Author(s):  
Tatjana Walter ◽  
Nour Al Medani ◽  
Arthur Burgardt ◽  
Katarina Cankar ◽  
Lenny Ferrer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Corynebacterium Glutamicum ◽  
Shikimate Pathway ◽  
Product Formation ◽  
Sugar Uptake ◽  
Bioreactor Culture ◽  
Acid Fermentation ◽  
Flavor Compound ◽  
Adenosyl Methionine

The N-functionalized amino acid N-methylanthranilate is an important precursor for bioactive compounds such as anticancer acridone alkaloids, the antinociceptive alkaloid O-isopropyl N-methylanthranilate, the flavor compound O-methyl-N-methylanthranilate, and as a building block for peptide-based drugs. Current chemical and biocatalytic synthetic routes to N-alkylated amino acids are often unprofitable and restricted to low yields or high costs through cofactor regeneration systems. Amino acid fermentation processes using the Gram-positive bacterium Corynebacterium glutamicum are operated industrially at the million tons per annum scale. Fermentative processes using C. glutamicum for N-alkylated amino acids based on an imine reductase have been developed, while N-alkylation of the aromatic amino acid anthranilate with S-adenosyl methionine as methyl-donor has not been described for this bacterium. After metabolic engineering for enhanced supply of anthranilate by channeling carbon flux into the shikimate pathway, preventing by-product formation and enhancing sugar uptake, heterologous expression of the gene anmt encoding anthranilate N-methyltransferase from Ruta graveolens resulted in production of N-methylanthranilate (NMA), which accumulated in the culture medium. Increased SAM regeneration by coexpression of the homologous adenosylhomocysteinase gene sahH improved N-methylanthranilate production. In a test bioreactor culture, the metabolically engineered C. glutamicum C1* strain produced NMA to a final titer of 0.5 g·L−1 with a volumetric productivity of 0.01 g·L−1·h−1 and a yield of 4.8 mg·g−1 glucose.

Sign in / Sign up

Export Citation Format

Share Document