Combinations of histone post-translational modifications

2021 ◽  
Vol 478 (3) ◽  
pp. 511-532
Author(s):  
Bethany C. Taylor ◽  
Nicolas L. Young
Keyword(s):  
Physiological State ◽  
The State ◽  
Eukaryotic Genome ◽  
Complex Signals ◽  
Post Translational Modifications ◽  
Essential Proteins ◽  
Histone Ptms ◽  
Multiple Variable ◽  
Combinatorial Function

Histones are essential proteins that package the eukaryotic genome into its physiological state of nucleosomes, chromatin, and chromosomes. Post-translational modifications (PTMs) of histones are crucial to both the dynamic and persistent regulation of the genome. Histone PTMs store and convey complex signals about the state of the genome. This is often achieved by multiple variable PTM sites, occupied or unoccupied, on the same histone molecule or nucleosome functioning in concert. These mechanisms are supported by the structures of ‘readers’ that transduce the signal from the presence or absence of PTMs in specific cellular contexts. We provide background on PTMs and their complexes, review the known combinatorial function of PTMs, and assess the value and limitations of common approaches to measure combinatorial PTMs. This review serves as both a reference and a path forward to investigate combinatorial PTM functions, discover new synergies, and gather additional evidence supporting that combinations of histone PTMs are the central currency of chromatin-mediated regulation of the genome.

scholarly journals A mass spectrometry-based assay using metabolic labeling to rapidly monitor chromatin accessibility of modified histone proteins

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Simone Sidoli ◽  
Mariana Lopes ◽  
Peder J. Lund ◽  
Naomi Goldman ◽  
Maria Fasolino ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chemical Properties ◽  
Chromatin Accessibility ◽  
Metabolic Labeling ◽  
Post Translational Modifications ◽  
Histone Ptms ◽  
Active Transcription ◽  
Or Gene ◽  
Histone Codes

Abstract Histone post-translational modifications (PTMs) contribute to chromatin accessibility due to their chemical properties and their ability to recruit enzymes responsible for DNA readout and chromatin remodeling. To date, more than 400 different histone PTMs and thousands of combinations of PTMs have been identified, the vast majority with still unknown biological function. Identification and quantification of histone PTMs has become routine in mass spectrometry (MS) but, since raising antibodies for each PTM in a study can be prohibitive, lots of potential is lost from MS datasets when uncharacterized PTMs are found to be significantly regulated. We developed an assay that uses metabolic labeling and MS to associate chromatin accessibility with histone PTMs and their combinations. The labeling is achieved by spiking in the cell media a 5x concentration of stable isotope labeled arginine and allow cells to grow for at least one cell cycle. We quantified the labeling incorporation of about 200 histone peptides with a proteomics workflow, and we confirmed that peptides carrying PTMs with extensively characterized roles in active transcription or gene silencing were in highly or poorly labeled forms, respectively. Data were further validated using next-generation sequencing to assess the transcription rate of chromatin regions modified with five selected PTMs. Furthermore, we quantified the labeling rate of peptides carrying co-existing PTMs, proving that this method is suitable for combinatorial PTMs. We focus on the abundant bivalent mark H3K27me3K36me2, showing that H3K27me3 dominantly represses histone swapping rate even in the presence of the more permissive PTM H3K36me2. Together, we envision this method will help to generate hypotheses regarding histone PTM functions and, potentially, elucidate the role of combinatorial histone codes.

scholarly journals A G(enomic)P(ositioning)S(ystem) for Plant RNAPII Transcription

2020 ◽  
Author(s):  
Sebastian Marquardt ◽  
Xueyuan Leng ◽  
Quentin Thomas ◽  
Simon Rasmussen
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Regulation Of Gene Expression ◽  
Positioning System ◽  
Biological Functions ◽  
Post Translational Modifications ◽  
Histone Ptms ◽  
Definition Of ◽  
Generation Sequencing ◽  
Rnapii Transcription

Post-translational modifications (PTMs) of histone residues shape the landscape of gene expression by modulating the dynamic process of RNAPII transcription. The contribution of particular histone modifications to the definition of distinct RNAPII transcription stages remains poorly characterized in plants. Chromatin Immuno-precipitation combined with next-generation sequencing (ChIP-seq) resolves the genomic distribution of histone modifications. Here, we review histone PTM ChIP-seq data in Arabidopsis thaliana and find support for a Genomic Positioning System (GPS) that guides RNAPII transcription. We review the roles of histone PTM “readers”, “writers” and “erasers”, with a focus on the regulation of gene expression and biological functions in plants. The distinct functions of RNAPII transcription during the plant transcription cycle may in part rely on the characteristic histone PTMs profiles that distinguish transcription stages.

scholarly journals Histone modifications during the life cycle of the brown alga Ectocarpus

2020 ◽  
Author(s):  
Simon Bourdareau ◽  
Leila Tirichine ◽  
Bérangère Lombard ◽  
Damarys Loew ◽  
Delphine Scornet ◽  
...  
Keyword(s):  
Life Cycle ◽  
Brown Algae ◽  
Land Plant ◽  
Chromatin Modifications ◽  
Post Translational Modifications ◽  
Transcription Start Sites ◽  
Histone Ptms ◽  
Genomic Regions ◽  
Active Genes

AbstractBackgroundBrown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expected to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here we have focused on mechanisms of epigenetic regulation involving post-translational modifications (PTMs) of histone proteins.ResultsA total of 47 histone PTMs were identified, including a novel mark H2AZR38me1, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identified PTMs associated with transcription start sites (TSSs) and gene bodies of active genes, and with transposons. H3K79me2 exhibited an unusual pattern, often marking large genomic regions spanning several genes. TSSs of closely spaced divergently transcribed gene pairs shared a common nucleosome depleted region and exhibited shared histone PTM peaks. Overall, patterns of histone PTMs were stable through the life cycle. Analysis of histone PTMs at generation-biased genes identified a correlation between the presence of specific chromatin marks and the level of gene expression.ConclusionsThe overview of histone PTMs in the brown algae presented here will provide a foundation for future studies aimed at understanding the role of chromatin modifications in the regulation of brown algal genomes.

scholarly journals Many Routes from Glycolysis to Histone PTMs. Nature “Matters Arising” response to: Zhang et al. Metabolic regulation of gene expression by histone lactylation. (2019) Nature. 574(7779), 575-580.

2020 ◽  
Author(s):  
Chaitanya A. Kulkarni ◽  
Paul Brookes
Keyword(s):  
Gene Expression ◽  
Small Molecule ◽  
Metabolic Regulation ◽  
Regulation Of Gene Expression ◽  
Histone Mark ◽  
Acetyl Coa ◽  
Post Translational Modifications ◽  
Histone Ptms

Multiple histone post-translational modifications (PTMs) originate from small molecule metabolites (e.g. acetyl-lysine from acetyl-CoA) 1. As such, we read with interest the recent Nature paper from Zhang et al. 2 reporting discovery of lysine lactylation as a novel histone mark originating from the metabolite lactate. However, several concerns arise regarding the identity and source of this novel PTM.

scholarly journals Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

2020 ◽  
Vol 9 (3) ◽  
pp. 640 ◽  
Author(s):  
Teresa Chioccarelli ◽  
Riccardo Pierantoni ◽  
Francesco Manfrevola ◽  
Veronica Porreca ◽  
Silvia Fasano ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sperm Quality ◽  
Critical Role ◽  
Human Sperm ◽  
Circular Rnas ◽  
Nuclear Condensation ◽  
Post Translational Modifications ◽  
Epigenetic Biomarkers ◽  
Histone Ptms ◽  
Non Coding Rnas

Spermatozoa (SPZ) are motile cells, characterized by a cargo of epigenetic information including histone post-translational modifications (histone PTMs) and non-coding RNAs. Specific histone PTMs are present in developing germ cells, with a key role in spermatogenic events such as self-renewal and commitment of spermatogonia (SPG), meiotic recombination, nuclear condensation in spermatids (SPT). Nuclear condensation is related to chromatin remodeling events and requires a massive histone-to-protamine exchange. After this event a small percentage of chromatin is condensed by histones and SPZ contain nucleoprotamines and a small fraction of nucleohistone chromatin carrying a landascape of histone PTMs. Circular RNAs (circRNAs), a new class of non-coding RNAs, characterized by a nonlinear back-spliced junction, able to play as microRNA (miRNA) sponges, protein scaffolds and translation templates, have been recently characterized in both human and mouse SPZ. Since their abundance in eukaryote tissues, it is challenging to deepen their biological function, especially in the field of reproduction. Here we review the critical role of histone PTMs in male germ cells and the profile of circRNAs in mouse and human SPZ. Furthermore, we discuss their suggested role as novel epigenetic biomarkers to assess sperm quality and improve artificial insemination procedure.

The role of metabolites and the role of histo-hematological barriers in the regulation of body functions. (End)

1937 ◽  
Vol 33 (5) ◽  
pp. 523-532
Author(s):  
L. S. Stern
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
General Circulation ◽  
Physiological State ◽  
The State ◽  
The Central Nervous System ◽  
The Brain ◽  
Physiological Systems

Evaluation of the results obtained in the study of the effect of cerebrospinal fluid on various physiological systems is complicated by the fact that the composition of the cerebrospinal fluid depends to a large extent on the state of the blood-brain barrier, and thus reflects not only a certain physiological state of the central nervous system. There is no doubt that the metabolic products of the brain, secreted into the cerebrospinal fluid, exert their effect not only on the activity of various parts of the brain and on the coordination of their functions, but due to the rapid transition of these substances from the cerebrospinal fluid into the general circulation, they also affect as a humoral a factor on the function of other physiological systems, as it was revealed in a number of experiments carried out in recent years in our laboratories. For example, it turned out that under various influences (direct irritation of the central nervous system in experimental epilepsy, irritation of the sensory nerves associated with severe pain, traumatic shock, toxemic or chemical shock, as well as starvation, prolonged insomnia, etc.) - substances appear in the cerebrospinal fluid that affect the state and activity of the cardiovascular system, the tone of smooth muscles, the excitability of the central nervous system, etc. These are the results of the work of our employees: Zeitlin, Weiss, Harles, Voskresensky, Gromakovskaya , Bazarova, Gotsman, Komarova and others. Work in this direction continues at the present time.

Predicting results of intra-sinus implantation

2021 ◽  
Vol 20 (3) ◽  
pp. 59-63
Author(s):  
М. А. Likhanova ◽  
◽  
К. А. Sivolapov ◽  
Keyword(s):  
Nasal Cavity ◽  
Maxillary Sinus ◽  
Mucociliary Clearance ◽  
Physiological State ◽  
The State ◽  
Factors Affecting ◽  
Functional Methods ◽  
Cone Beam Computerized Tomography ◽  
Maxillary Sinuses

The study included 564 patients with a deficit in the volume of bone tissue of the alveolar process of the maxillary bone, which did not allow simultaneous installation of crestal implants. The work was carried out relying on modern forecasting systems based on an aggregate and quantitative assessment of the risk of intra- and postoperative complications, anatomical and physiological state of tissues and organs in the area of intervention. In the course of the study, a system for predicting the results of subaxillary augmentation was developed. Factors affecting the nature and frequency of complications in the immediate and long-term postoperative periods are highlighted. A comparative assessment of the functioning of the mucociliary clearance depending on the volume and location of the augmentate is given. Functional methods of investigation – spiral computed tomography and cone-beam computerized tomography – of maxillary bones, video endoscopy of the nasal cavity, study of mucociliary clearance, anterior active rhinomanometry were used. The assessment of the state of the augmentate, pneumatization of the maxillary sinuses, the anatomy of the nasal cavity, paranasal sinuses, the state of the maxillary sinus mucosa, the vertical volume of the walls of the maxillary sinus, and the evacuation capacity of the maxillary sinuses were evaluated. A score was determined for each of the studied parameters. Patterns of preoperative changes in the maxillary sinuses that led to complications in the postoperative period were identified. For each of these parameters, the amount of points collected can range from 1 to 5 points. The higher the score, the higher the probability of successful surgical treatment. If the sum of points is from 1 to 2, forecast of subaxillary augmentation is unfavourable, for 3 points is questionable, with a score of 4–5, the prognosis is favourable.

scholarly journals A genetic analysis reveals novel histone residues required for transcriptional reprogramming upon stress

2020 ◽  
Vol 48 (7) ◽  
pp. 3455-3475
Author(s):  
Cristina Viéitez ◽  
Gerard Martínez-Cebrián ◽  
Carme Solé ◽  
René Böttcher ◽  
Clement M Potel ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Growth Conditions ◽  
Proof Of Concept ◽  
Transcriptional Program ◽  
Post Translational Modifications ◽  
Transcriptional Reprogramming ◽  
Histone Ptms ◽  
Response To Stress ◽  
State Growth

Abstract Cells have the ability to sense, respond and adapt to environmental fluctuations. Stress causes a massive reorganization of the transcriptional program. Many examples of histone post-translational modifications (PTMs) have been associated with transcriptional activation or repression under steady-state growth conditions. Comparatively less is known about the role of histone PTMs in the cellular adaptive response to stress. Here, we performed high-throughput genetic screenings that provide a novel global map of the histone residues required for transcriptional reprogramming in response to heat and osmotic stress. Of note, we observed that the histone residues needed depend on the type of gene and/or stress, thereby suggesting a ‘personalized’, rather than general, subset of histone requirements for each chromatin context. In addition, we identified a number of new residues that unexpectedly serve to regulate transcription. As a proof of concept, we characterized the function of the histone residues H4-S47 and H4-T30 in response to osmotic and heat stress, respectively. Our results uncover novel roles for the kinases Cla4 and Ste20, yeast homologs of the mammalian PAK2 family, and the Ste11 MAPK as regulators of H4-S47 and H4-T30, respectively. This study provides new insights into the role of histone residues in transcriptional regulation under stress conditions.

scholarly journals Удосконалення умов утримання кнурів закордонної селекції, вплив моціону на виробництво сперми

2018 ◽  
Author(s):  
А. С. Федяєва
Keyword(s):  
Private Enterprise ◽  
Physiological State ◽  
The State ◽  
State Enterprise ◽  
The Impact

У статті наведено матеріали про використання моціону та удосконалення технологічних умов утримання кнурів зарубіжної селекції. Також вивчено вплив моціону на виробництво та якість сперми в умовах діючого господарства ДП «Націонал Плюс» ПП «Націонал» Дніпропетровської області. Встановили, що впровадження моціону та удосконалення умов утримання кнурів закордонної селекції позитивно вплинуло на фізіологічний стан кнурів, що призвело до покращання якості сперми. В умовах господарства виявлено кращі зарубіжні генотипи кнурів-плідників, основними з яких є термінальні кнури лінії Macster (канадської селекції), які за всіма показниками переважали всі інші. In the article materials are given on the use of exercise and the improvement of technological conditions for keeping of boars of foreign selection. Also the impact of the exercise on the production and quality of semen under the conditions of the current economy of the state enterprise «National Plus» of the private enterprise «National» of the Dnipropetrovsk region was studied. We established that the introduction of the exercise and the improvement of the conditions of keeping of boars of foreign breeding positively influenced on the physiological state of the boars, which led to an improvement in the quality of the sperm. Also in the conditions of farming, the best genotypes of boars-producers are revealed.  One of the main is the terminal boars of the Macster line (Canadian breeding), which in all respects exceeded all other boars.

Physiological state of the sterlet × beluga hybrid (Asipenser ruthenus × Huso huso) when growing under ecological conditions in the Volga delta

2020 ◽  
pp. 41-52
Author(s):  
Svetlana Sergeevna Astafyeva ◽  
Alexander Robertovich Lozovskiy
Keyword(s):  
Serum Albumin ◽  
Total Protein ◽  
Physiological State ◽  
Serum Triglyceride ◽  
Blood Parameters ◽  
The State ◽  
Physiological Adaptation ◽  
Huso Huso ◽  
Volga Delta ◽  
Iron Analysis

Three-year-olds (15 individuals) and eight-year-olds (15 individuals) of the sterlet × beluga hybrid (Asipenser ruthenus × Huso huso), grown in mesh cages in the Volga delta, were studied in the third decade of September 2019 in order to establish the functional state of the organism by blood parameters reflecting the state erythron and metabolism. The results of the performed study found that the erythron system differs in a smaller number of blood erythrocytes in eight-year-olds (0,76 ± 0,04 × 1012l –1) compared with three-year-olds (0,98 ± 0,04 × 1012l –1), in the absence of differences in blood hemoglobin and serum iron. Analysis of the state of protein metabolism showed that the content of total protein and the activity of ASAT in serum were the same in the groups. The serum albumin content in eight-yearolds was 17,87 ± 0,92 g/l, which was significantly less than in three-year-olds (24,15 ± 1,78) (p < 0,05). The relative content of serum albumin (as a percentage of total protein) in eightyear-olds was 51,04 ± 3,12%, which is less than in three-year-olds (72,51 ± 6,04%) (p < 0.01). The serum ALAT activity in eight-year-olds was lower than in three-year-olds (2,33 ± 0,16 and 2,93 ± 0,17 μkat/l, respectively) (p < 0,05). The results of the study of lipid metabolism revealed that serum cholesterol in eight-year-olds (2,62 ± 0,11 mmol/l) is less than in three-year-olds (1,39 ± 0,05) (p < 0,05). However, the serum triglyceride content did not differ between threeyear-olds and eight-year-olds, being 3,50 ± 0,07 and 3,26 ± 0,13 mmol/l, respectively. The glycemic values in three-year-olds and eight-year-olds are significantly different and amount to 1,80 ± 0,08 and 1,42 ± 0,11 mmol/l, respectively (p < 0.05). The results of the study can be used to assess the state of physiological adaptation of the hybrid and to determine the reference values of the parameters of the erythron system and metabolic homeostasis.

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