Biology subjects

Schulz, R.

Publications and source records attributed to Schulz, R..

24 records · Page 2Linked to original sources

bioRxiv2020

Ush regulates hemocyte-specific gene expression, fatty acid metabolism and cell cycle progression and cooperates with dNuRD to orchestrate hematopoiesis

The generation of lineage-specific gene expression programmes that alter proliferation capacity, metabolic profile and cell type-specific functions during differentiation from multipotent stem cells to specialised cell types is crucial for development. During differentiation gene expression programmes are dynamically modulated by a complex interplay between sequence-specific transcription factors, associated cofactors and epigenetic regulators. Here, we study U-shaped (Ush), a multi-zinc finger protein that maintains the multipotency of stem cell-like hemocyte progenitors during Drosophila hematopoiesis. Using genomewide approaches we reveal that Ush binds to promoters and enhancers and that it controls the expression of three gene classes that encode proteins relevant to stem cell-like functions and differentiation: cell cycle regulators, key metabolic enzymes and proteins conferring specific functions of differentiated hemocytes. We employ complementary biochemical approaches to characterise the molecular mechanisms of Ush-mediated gene regulation. We uncover distinct Ush isoforms one of which binds the Nucleosome Remodeling and Deacetylation (NuRD) complex using an evolutionary conserved peptide motif. Remarkably, the Ush/NuRD complex specifically contributes to the repression of lineage-specific genes but does not impact the expression of cell cycle regulators or metabolic genes. This reveals a mechanism that enables specific and concerted modulation of functionally related portions of a wider gene expression programme. Finally, we use genetic assays to demonstrate that Ush and NuRD regulate enhancer activity during hemocyte differentiation in vivo and that both cooperate to suppress the differentiation of lamellocytes, a highly specialised blood cell type. Our findings reveal that Ush coordinates proliferation, metabolism and cell type-specific activities by isoform-specific cooperation with an epigenetic regulator.

molecular biology↗

bioRxiv2020

Transcription of intragenic CpG islands influences spatiotemporal host gene pre-mRNA processing

Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic factors such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes exhibit dynamic epigenetic and gene expression patterns during development and between different tissues. We hypothesise that iCGI-associated H3K36me3, DNA methylation and transcription can influence host gene AS and/or APA. We investigate H3K36me3 and find that this histone mark is not a major regulator of AS or APA in our model system. Genomewide, we identify over 4000 host genes that harbour an iCGI in the mammalian genome, including both previously annotated and novel iCGI/host gene pairs. The transcriptional activity of these iCGIs is tissue- and developmental stage-specific and, for the first time, we demonstrate that the premature termination of host gene transcripts upstream of iCGIs is closely correlated with the level of iCGI transcription in a DNA-methylation independent manner. These studies suggest that iCGI transcription, rather than H3K36me3 or DNA methylation, interfere with host gene transcription and pre-mRNA processing genomewide and contributes to the spatiotemporal diversification of both the transcriptome and proteome.

molecular biology↗

bioRxiv2020

Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones

Cell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA (rRNA) are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 (MMP-2) was previously detected in the nucleus. However, its role there is elusive. Herein we report that MMP-2 resides within the nucleolus to regulate rRNA transcription. MMP-2 is enriched at the promoter region of rRNA gene repeats and its inhibition downregulates pre-rRNA transcription. The N-terminal tail of histone H3 is clipped by MMP-2 in the nucleolus and is associated with increased rRNA transcription. Knocking down/out MMP-2 or inhibiting its activity prevents histone H3 cleavage and reduces both rRNA transcription and cell proliferation. In addition to the known extracellular roles of MMP-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar MMP-2 regulates cell proliferation through histone proteolysis and facilitation of rRNA transcription.

cell biology↗

bioRxiv2019

Reduced frontal white matter microstructure in healthy older adults with low tactile recognition performance

Aging leads to a reduction of connectivity in large-scale structural brain networks. Sensory processing and other cognitive processes rely on information flow between distant brain areas. However, data linking age-related structural brain alterations to cognitive functioning, especially sensory processing, is sparse.\n\nAiming to determine group differences in sensory processing between older and younger participants, we implemented a complex tactile recognition task and investigated to what extent changes in microstructural white matter integrity of large-scale brain networks might reflect success in task performance. Structural brain integrity was accessed by means of diffusion-weighted imaging and fractional anisotrophy.\n\nThe data revealed that poor performance in complex tactile recognition in older, neurologically healthy individuals is related to decreased structural integrity pronounced in the anterior corpus callosum. This region was strongly connected to the prefrontal cortex. Our data suggests decreased fractional anisotrophy in the anterior corpus callosum as a surrogate marker for progressed brain aging, leading to disturbances in networks relevant for higher-order cognitive processing. Complex tactile recognition might be a sensitive marker for identifying these starting cognitive impairments in older adults.

neuroscience↗

bioRxiv2019

Effects of transcranial alternating-current stimulation to secondary motor areas on cortical oscillations in stroke patients

BackgroundThere is growing evidence that secondary motor areas are relevant for recovery after motor stroke. Communication among brain areas occurs via synchronization of oscillatory activity which can potentially be modulated via transcranial alternating-current stimulation (tACS).\n\nHypothesisWe hypothesized that tACS to secondary motor areas of the stroke-lesioned hemisphere leads to modulation of task-related connectivity among primary and secondary motor areas, reflected in metrics of EEG coupling in the frequency domain.\n\nMethodsWe applied focal tACS at 1mA peak-to-peak intensity to ipsilesional ventral premotor cortex (PMv) and supplementary motor area (SMA) in chronic stroke patients while they moved their impaired hand. To probe effects of stimulation on cortical oscillations, several task-related EEG-based connectivity metrics (coherence, imaginary coherence, phase-locking value, mutual information) were assessed before and after each stimulation.\n\nResultsOverall, we found significant but weak modulations of the motor network by tACS. Stimulation of PMv reduced task-related coupling between (i) both primary motor cortices (M1) (coherence, -0.0514{+/-}0.0665 (mean{+/-}SD, active stimulation) vs. 0.0085{+/-}0.0888 (sham), p=0.0029) and (ii) between ipsilesional M1 and contralesional PMv (coherence, - 0.0386{+/-}0.0703 vs. 0.0226{+/-}0.0694, p=0.0283; phase-locking value, -0.0363{+/-}0.0581 vs. 0.0036{+/-}0.0497, p=0.0097) compared with sham stimulation.\n\nConclusionsIn this exploratory analysis, tACS to the ipsilesional PMv induced a weak decrease of task-related connectivity between ipsilesional M1 and contralesional M1 and PMv. As an excess of interhemispheric coupling is under discussion as maladaptive phenomenon of motor reorganization after stroke (e.g., bimodal balance-recovery model), tACS-induced reduction of coupling might be an interesting approach to assist re-normalization of the post-stroke motor network.

neuroscience↗

bioRxiv2018

In-depth investigation of the species problem and taxonomic status of marbled crayfish, the first asexual decapod crustacean

The marbled crayfish is the only obligately parthenogenetic decapod crustacean and a novel research model and invasive animal on three continents. It is regarded either as a parthenogenetic form of slough crayfish Procambarus fallax or as a separate species named Procambarus virginalis. In order to investigate the species question of this unusual crayfish in detail we have identified the similarities and differences in morphology, life history, genetics, behaviour, ecology and biogeography between marbled crayfish and its most likely parent species P. fallax. We have investigated specimens from natural habitats, laboratory colonies and museum collections and performed a meta-analysis of our data and published data. Our COI based molecular tree with 27 Cambaridae confirms closest relationship of marbled crayfish with P. fallax. Marbled crayfish and P. fallax are similar with respect to morphological characters, coloration and body proportions, but differ considerably with respect to body size, fertility and longevity. The mitochondrial genes of both crayfish are similar, but ploidy level and haploid genome size are markedly different. Both crayfish are eurytopic and have two major annual recruitment periods, but marbled crayfish show different population structure and higher invasiveness. Marbled crayfish occur in tropical to cold temperate habitats of the old world, but P. fallax is confined to subtropical and warm-temperate habitats of the southeastern USA. Cross-breeding experiments with both crayfish revealed reproductive isolation. The application of the Evolutionary Genetic Species Concept for asexuals to all available data supports raising marbled crayfish from \"forma\" to species rank. A determination key is provided to discriminate Procambarus virginalis, the first asexual decapod species, from its parent species P. fallax.

zoology↗