ABSTRACT
Dosage compensation, mediated by the MSL complex, regulates X-chromosomal gene expression in Drosophila. Here we report that the histone H4 lysine 16 (H4K16) specific histone acetyltransferase MOF displays differential binding behavior depending on whether the target gene is located on the X chromosome versus the autosomes. More specifically, on the male X chromosome, where MSL1 and MSL3 are preferentially associated with the 3' end of dosage compensated genes, MOF displays a bimodal distribution binding to promoters and the 3' ends of genes. In contrast, on MSL1/MSL3 independent X-linked genes and autosomal genes in males and females, MOF binds primarily to promoters. Binding of MOF to autosomes is functional, as H4K16 acetylation and the transcription levels of a number of genes are affected upon MOF depletion. Therefore, MOF is not only involved in the onset of dosage compensation, but also acts as a regulator of gene expression in the Drosophila genome.
Subject(s)
Dosage Compensation, Genetic , Drosophila Proteins/metabolism , Gene Expression Regulation , Histone Acetyltransferases/metabolism , Nuclear Proteins/metabolism , 3' Flanking Region , Acetylation , Animals , Cell Line , Female , Genome, Insect , Histones/genetics , Histones/metabolism , Male , Promoter Regions, Genetic , X ChromosomeABSTRACT
Effective science communication is fundamental to closing the gap from research and innovation to clinical implementation. Existing paradigms of science communication are often challenged by a lack of skill and engagement, particularly from those who progress the science. Currently, a standardized curriculum on science communication, with global applicability, does not exist. The purpose of this project is to address the gap in training by health professionals and clinical researchers through the development of a globally relevant curriculum for science communication. The nominal group technique (NGT) was used whereby a convenience sample of eleven science communication experts from across the globe generated, discussed, and arrived at a consensus on topics that should be included in a standardized science communication curriculum. Experts represented diverse backgrounds within the health sciences. Due to the COVID-19 pandemic and geographical constraints, the NGT was conducted virtually. The consensus-building methodology allowed for each expert to equally present ideas and collaborate with one another to create a robust and comprehensive curriculum for effective science communication. Expert panelists reached a consensus on 10 essential components of a standardized global science communication curriculum. Following the refinement of the curriculum topic areas, a virtual meeting with project co-investigators was held to review the topics and discuss relevance, applicability, and appeal to the local contexts. A standardized science communication curriculum is needed for health professionals and clinical researchers. The NGT achieved expert consensus on the core topics. The next steps are to develop the course ensuring optimal participation from learners across the globe.
Subject(s)
COVID-19 , Pandemics , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Health Personnel/education , Curriculum , CommunicationABSTRACT
Wild relatives of crops thrive in habitats where environmental conditions can be restrictive for productivity and survival of cultivated species. The genetic basis of this variability, particularly for tolerance to high temperatures, is not well understood. We examined the capacity of wild and cultivated accessions to acclimate to rapid temperature elevations that cause heat stress (HS). We investigated genotypic variation in thermotolerance of seedlings of wild and cultivated accessions. The contribution of polymorphisms associated with thermotolerance variation was examined regarding alterations in function of the identified gene. We show that tomato germplasm underwent a progressive loss of acclimation to strong temperature elevations. Sensitivity is associated with intronic polymorphisms in the HS transcription factor HsfA2 which affect the splicing efficiency of its pre-mRNA. Intron splicing in wild species results in increased synthesis of isoform HsfA2-II, implicated in the early stress response, at the expense of HsfA2-I which is involved in establishing short-term acclimation and thermotolerance. We propose that the selection for modern HsfA2 haplotypes reduced the ability of cultivated tomatoes to rapidly acclimate to temperature elevations, but enhanced their short-term acclimation capacity. Hence, we provide evidence that alternative splicing has a central role in the definition of plant fitness plasticity to stressful conditions.
Subject(s)
Alternative Splicing/genetics , Domestication , Genetic Variation , RNA Precursors/genetics , Solanum lycopersicum/genetics , Solanum lycopersicum/physiology , Thermotolerance/genetics , Acclimatization , Alleles , Base Sequence , Genome-Wide Association Study , Haplotypes/genetics , Heat-Shock Response , Introns/genetics , Polymorphism, Genetic , Protein Isoforms/metabolism , Protein Stability , Protein Transport , RNA Precursors/metabolism , Seedlings/physiology , TemperatureABSTRACT
Here, we report the biochemical characterization of the nonspecific lethal (NSL) complex (NSL1, NSL2, NSL3, MCRS2, MBD-R2, and WDS) that associates with the histone acetyltransferase MOF in both Drosophila and mammals. Chromatin immunoprecipitation-Seq analysis revealed association of NSL1 and MCRS2 with the promoter regions of more than 4000 target genes, 70% of these being actively transcribed. This binding is functional, as depletion of MCRS2, MBD-R2, and NSL3 severely affects gene expression genome wide. The NSL complex members bind to their target promoters independently of MOF. However, depletion of MCRS2 affects MOF recruitment to promoters. NSL complex stability is interdependent and relies mainly on the presence of NSL1 and MCRS2. Tethering of NSL3 to a heterologous promoter leads to robust transcription activation and is sensitive to the levels of NSL1, MCRS2, and MOF. Taken together, we conclude that the NSL complex acts as a major transcriptional regulator in Drosophila.
Subject(s)
Drosophila Proteins/metabolism , Drosophila/metabolism , Histone Acetyltransferases/metabolism , Nuclear Proteins/metabolism , Animals , Drosophila/genetics , Drosophila Proteins/genetics , Genome, Insect , Histone Acetyltransferases/genetics , Multiprotein Complexes/genetics , Multiprotein Complexes/metabolism , Nuclear Proteins/genetics , Promoter Regions, Genetic , Protein Binding , Transcription, GeneticABSTRACT
Since 2010, the European Molecular Biology Laboratory's (EMBL) Heidelberg laboratory and the European Bioinformatics Institute (EMBL-EBI) have jointly run bioinformatics training courses developed specifically for secondary school science teachers within Europe and EMBL member states. These courses focus on introducing bioinformatics, databases, and data-intensive biology, allowing participants to explore resources and providing classroom-ready materials to support them in sharing this new knowledge with their students. In this article, we chart our progress made in creating and running three bioinformatics training courses, including how the course resources are received by participants and how these, and bioinformatics in general, are subsequently used in the classroom. We assess the strengths and challenges of our approach, and share what we have learned through our interactions with European science teachers.
Subject(s)
Biology/education , Computational Biology , TeachingABSTRACT
In movement analysis, correlated random walk (CRW) models often use so-called turning angles, which are measured relative to the previous movement direction. To segregate between different movement modes, hidden Markov models (HMMs) describe movements as piecewise stationary CRWs in which the distributions of turning angles and step sizes depend on the underlying state. This typically allows for the segregation of movement modes that show different movement speeds. We show that in some cases, it may be interesting to investigate absolute angles, that is, biased random walks (BRWs) instead of turning angles. In particular, while discrimination between states in the turning angle setting can only rely on movement speed, models with absolute angles can be used to discriminate between sections of different movement directions. A preprocessing algorithm is provided that enables the analysis of absolute angles in the existing R package moveHMM. In a data set of movements of cell organelles, models using not the turning angle but the absolute angle could capture interesting additional properties. Goodness-of-fit was increased for HMMs with absolute angles, and HMMs with absolute angles tended to choose a higher number of states, suggesting the existence and relevance of prominent directional changes in the present data set. These results suggest that models with absolute angles can provide important information in the analysis of movement patterns if the existence and frequency of directional changes is of biological importance.
ABSTRACT
Plants respond to higher temperatures by the action of heat stress (HS) transcription factors (Hsfs), which control the onset, early response, and long-term acclimation to HS. Members of the HsfA1 subfamily, such as tomato HsfA1a, are the central regulators of HS response, and their activity is fine-tuned by other Hsfs. We identify tomato HsfA7 as capacitor of HsfA1a during the early HS response. Upon a mild temperature increase, HsfA7 is induced in an HsfA1a-dependent manner. The subsequent interaction of the two Hsfs prevents the stabilization of HsfA1a resulting in a negative feedback mechanism. Under prolonged or severe HS, HsfA1a and HsfA7 complexes stimulate the induction of genes required for thermotolerance. Therefore, HsfA7 exhibits a co-repressor mode at mild HS by regulating HsfA1a abundance to moderate the upregulation of HS-responsive genes. HsfA7 undergoes a temperature-dependent transition toward a co-activator of HsfA1a to enhance the acquired thermotolerance capacity of tomato plants.
Subject(s)
Heat Shock Transcription Factors/genetics , Solanum lycopersicum/genetics , Trans-Activators/genetics , Acclimatization , Arabidopsis , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , DNA-Binding Proteins/metabolism , Gene Expression/genetics , Gene Expression Regulation, Plant/genetics , Heat Shock Transcription Factors/metabolism , Heat-Shock Proteins/metabolism , Heat-Shock Response/genetics , Hot Temperature , Solanum lycopersicum/metabolism , Plant Proteins/genetics , Plants, Genetically Modified/metabolism , Thermotolerance/genetics , Trans-Activators/metabolism , Transcription Factors/metabolismABSTRACT
INTRODUCTION: This study determined the amount and severity of EARR (external apical root resorption) after orthodontic treatment with self-ligating (SL) and conventional (Non-SL) brackets. Differences regarding rate of extraction cases, appointments and treatment time were evaluated. MATERIAL AND METHODS: 213 patients with a mean age of 12.4 ± 2.2 years were evaluated retrospectively. The treatments were performed with SL brackets (n = 139, Smartclip, 3 M Unitek, USA) or Non-SL brackets (n = 74, Victory Series, 3 M Unitek, USA). Measurements of the crown and root length of the incisors were taken using panoramic radiographs. Three-factor analysis of variance (ANOVA) was performed for an appliance effect. RESULTS: There was no difference between patients treated with Non-SL or SL brackets regarding the amount (in percentage) of EARR (Non-SL: 4.5 ± 6.6 vs. SL: 3.0 ± 5.6). Occurrence of severe EARR (sEARR) did also not differ between the two groups (Non-SL 0.5 vs. SL: 0.3). The percentage of patients with need of tooth extraction for treatment (Non SL: 8.1 vs. SL: 6.9) and the number of appointments (Non-SL: 12.4 ± 3.4 vs. SL: 13.9 ± 3.3) did not show any differences. The treatment time was shorter with Non-SL brackets (Non-SL: 18.1 ± 5.3 vs. SL: 20.7 ± 4.9 months). CONCLUSIONS: This is the largest study showing that there is no difference in the amount of EARR, number of appointments and extraction rate between conventional and self-ligating brackets. For the first time we could demonstrate that occurrence of sEARR does not differ between the two types of brackets.
Subject(s)
Orthodontic Brackets , Orthodontics, Corrective/instrumentation , Root Resorption , Tooth Apex/pathology , Adolescent , Child , Equipment Design , Female , Humans , Ligation , Male , Malocclusion/therapy , Radiography, Panoramic , Retrospective Studies , Root Resorption/diagnostic imaging , Stress, Mechanical , Tooth Apex/diagnostic imaging , Tooth Extraction , Tooth Movement Techniques/instrumentationABSTRACT
Dosage compensation in Drosophila is dependent on MSL proteins and involves hypertranscription of the male X chromosome, which ensures equal X-linked gene expression in both sexes. Here, we report the purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells. We find a stable association of the histone H4 lysine 16-specific acetyltransferase MOF with the RNA/protein containing MSL complex as well as with an evolutionary conserved complex. We show that the MSL complex interacts with several components of the nuclear pore, in particular Mtor/TPR and Nup153. Strikingly, knockdown of Mtor or Nup153 results in loss of the typical MSL X-chromosomal staining and dosage compensation in Drosophila male cells but not in female cells. These results reveal an unexpected physical and functional connection between nuclear pore components and chromatin regulation through MSL proteins, highlighting the role of nucleoporins in gene regulation in higher eukaryotes.