Most multi-cellular organisms adopt a specific gene expression pattern during cellular differentiation. Once established, this pattern is frequently maintained over several cell divisions despite the ...fact that the initiating signal is no longer present. Differential packaging into chromatin is one such mechanism that allows fixation of transcriptional activity. Recent genome-wide studies demonstrate that actively transcribed regions are characterized by a specific modification pattern of histones, the main protein component of chromatin. These findings support the hypothesis that a histone code uses histone post-translational modifications to stably inscribe particular chromatin structures into the genome. Experiments on the dynamics of histone modifications reveal a striking kinetic difference between methylation, phosphorylation and acetylation, suggesting different roles of these modifications in epigenetically fixing specific gene expression patterns.
Constitutive heterochromatin is typically defined by high levels of DNA methylation and H3 lysine 9 trimethylation (H3K9Me3), whereas facultative heterochromatin displays DNA hypomethylation and high ...H3 lysine 27 trimethylation (H3K27Me3). The two chromatin types generally do not coexist at the same loci, suggesting mutual exclusivity. During development or in cancer, pericentromeric regions can adopt either epigenetic state, but the switching mechanism is unknown. We used a quantitative locus purification method to characterize changes in pericentromeric chromatin-associated proteins in mouse embryonic stem cells deficient for either the methyltransferases required for DNA methylation or H3K9Me3. DNA methylation controls heterochromatin architecture and inhibits Polycomb recruitment. BEND3, a protein enriched on pericentromeric chromatin in the absence of DNA methylation or H3K9Me3, allows Polycomb recruitment and H3K27Me3, resulting in a redundant pathway to generate repressive chromatin. This suggests that BEND3 is a key factor in mediating a switch from constitutive to facultative heterochromatin.
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•PICh reveals pericentromeric heterochromatin-associated proteins in ESCs•H3K9me3 controls maintenance DNA methylation and the chromosomal passenger complex•DNA methylation controls pericentromeric architecture and Polycomb binding•BEND3 mediates Polycomb recruitment in the absence of H3K9Me3 or DNA methylation
Saksouk et al. use a quantitative version of the Proteomics of Isolated Chromatin segment method to establish pericentromeric heterochromatin composition and analyze how H3K9me3 and DNA methylation regulate this locus in embryonic stem cells. A model in which methylation-sensitive DNA binding proteins control the switching of the locus into distinct epigenetic states is proposed.
Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin ...capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment of these marks extends over several cell generations. Together, our results reveal how histone marks propagate and demonstrate that chromatin states oscillate within the cell cycle.
Vibrio cholerae-specific bacteriophages are common features of the microbial community during cholera infection in humans. Phages impose strong selective pressure that favors the expansion of ...phage-resistant strains over their vulnerable counterparts. The mechanisms allowing virulent V. cholerae strains to defend against the ubiquitous threat of predatory phages have not been established. Here, we show that V. cholerae PLEs (phage-inducible chromosomal island-like elements) are widespread genomic islands dedicated to phage defense. Analysis of V. cholerae isolates spanning a 60-year collection period identified five unique PLEs. Remarkably, we found that all PLEs (regardless of geographic or temporal origin) respond to infection by a myovirus called ICP1, the most prominent V. cholerae phage found in cholera patient stool samples from Bangladesh. We found that PLE activity reduces phage genome replication and accelerates cell lysis following ICP1 infection, killing infected host cells and preventing the production of progeny phage. PLEs are mobilized by ICP1 infection and can spread to neighboring cells such that protection from phage predation can be horizontally acquired. Our results reveal that PLEs are a persistent feature of the V. cholerae mobilome that are adapted to providing protection from a single predatory phage and advance our understanding of how phages influence pathogen evolution.
Abstract
The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74
μ
eV to 22.47
μ
eV mass range. The detection concept follows the ...Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to
g
a
γ
γ
= 8 × 10
−14
GeV
−1
at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.
Background
Urinary proteomics identifies the totality of urinary proteins and can therefore help in getting an early and precise diagnosis of various pathological processes in the kidneys. In ...infants, non-invasive urine collection is most commonly accomplished with a urine bag or clean catch. The influence of those two collection methods on urinary proteomics was assessed in this study.
Methods
Thirty-two urine samples were collected in infants using urine bag and clean catch within 24 h. Nine boys and seven girls with a mean age of 4.3 ± 2.9 months were included (5 × post-pyelonephritis, 10 × non-kidney disease, 1 × chronic kidney disease (CKD)). Liquid chromatography-mass spectrometry (LC–MS/MS) was performed in data-independent acquisition (DIA) mode. Protein identification and quantification were achieved using Spectronaut.
Results
A total of 1454 urinary proteins were detected. Albumin and α-1-microglobulin were detected the most. The 18 top-abundant proteins accounted for 50% of total abundance. The number of proteins was slightly, but insignificantly higher in clean catch (957 ± 245) than in bag urine (876 ± 255). The median intensity was 1.2 × higher in the clean catch. Overall, differential detection of proteins was 29% between the collection methods; however, it diminished to 3% in the 96 top-abundant proteins. Pearson’s correlation coefficient was 0.81 ± 0.11, demonstrating a high intraindividual correlation. A principal component analysis and a heat map showed clustering according to diagnoses and patients rather than to the collection method.
Conclusion
Urinary proteomics shows a high correlation with minor variation in low-abundant proteins between the two urine collection methods. The biological characteristics overrule this variation.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
.
Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their host's fitness. The phage-inducible chromosomal island-like element (PLE) is a mobile ...element that integrates into the chromosome of Vibrio cholerae and parasitizes the bacteriophage ICP1 to move between cells. This parasitism by PLE is such that it abolishes the production of ICP1 progeny and provides a defensive boon to the host cell population. In response to the severe parasitism imposed by PLE, ICP1 has acquired an adaptive CRISPR-Cas system that targets the PLE genome during infection. However, ICP1 isolates that naturally lack CRISPR-Cas are still able to overcome certain PLE variants, and the mechanism of this immunity against PLE has thus far remained unknown. Here, we show that ICP1 isolates that lack CRISPR-Cas encode an endonuclease in the same locus, and that the endonuclease provides ICP1 with immunity to a subset of PLEs. Further analysis shows that this endonuclease is of chimeric origin, incorporating a DNA-binding domain that is highly similar to some PLE replication origin-binding proteins. This similarity allows the endonuclease to bind and cleave PLE origins of replication. The endonuclease appears to exert considerable selective pressure on PLEs and may drive PLE replication module swapping and origin restructuring as mechanisms of escape. This work demonstrates that new genome defense systems can arise through domain shuffling and provides a greater understanding of the evolutionary forces driving genome modularity and temporal succession in mobile elements.
Public demand for food produced in systems with high animal welfare standards is rising. In terms of animal welfare, the dairy industry has a positive reputation in European countries. However, there ...are many practices in the dairy industry of which the public is unaware, e.g.
,
zero-grazing, tethering, dehorning, disposal of male calves, and early cow-calf separation. We focused on the latter and reviewed studies addressing public opinions about dealing with calves in dairy farming. We show that most respondents in studies are unaware or reject these practices. During the last years, more and more attention was paid to cow-calf separation. This practice is mainly rejected because it is considered to be unnatural and associated with stress for the animals. However, there is a lack of scientific surveys that explore the public opinion about how much stress is tolerable in animals that have been allowed to live up to their needs for a period of time. On the other hand, the economic aspects of management practices enabling the animals to express their natural behavior to a greater extent than in the current husbandry systems should be investigated comprehensively. The amount of sales and the willingness to pay a higher price for milk and meat produced in such systems might be the key factors to a wider acceptance of such systems by dairy farmers, who will expect to be compensated for their increased efforts.
A
bstract
We present results of the Relic Axion Dark-Matter Exploratory Setup (RADES), a detector which is part of the CERN Axion Solar Telescope (CAST), searching for axion dark matter in the 34.67
...μ
eV mass range. A radio frequency cavity consisting of 5 sub-cavities coupled by inductive irises took physics data inside the CAST dipole magnet for the first time using this filter-like haloscope geometry. An exclusion limit with a 95% credibility level on the axion-photon coupling constant of g
aγ
≳ 4 × 10
−
13
GeV
−
1
over a mass range of 34
.
6738
μ
eV
< m
a
<
34
.
6771
μ
eV is set. This constitutes a significant improvement over the current strongest limit set by CAST at this mass and is at the same time one of the most sensitive direct searches for an axion dark matter candidate above the mass of 25
μ
eV. The results also demonstrate the feasibility of exploring a wider mass range around the value probed by CAST-RADES in this work using similar coherent resonant cavities.
The article presents an online learning approach for a cognitive framework for classification. The classification process is realised via sequential illuminations with different waveforms and ...modelled by partially observable Markov decision processes. Since the operational environment is not accessible, the agent is trained on a similar one. The difference between the trained and operational environment is learned without external knowledge and an existing model. In a first step, the capability of this new approach is shown on generic data. In a second step, it is used on high fidelity simulated data and different waveforms that create high resolution range profiles. The tests on the scenario with electromagnetic models, show noticeable improvement in comparison to the framework without learning capability.
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