A5016513207- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Genetic Associations and Epidemiology
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Neurogenesis and neuroplasticity mechanisms
- Pluripotent Stem Cells Research
- interferon and immune responses
- Receptor Mechanisms and Signaling
- Congenital heart defects research
- Genomic variations and chromosomal abnormalities
- Neuroendocrine regulation and behavior
- Cytokine Signaling Pathways and Interactions
- Single-cell and spatial transcriptomics
- Nerve injury and regeneration
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Memory and Neural Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Diet and metabolism studies
- Genetics, Bioinformatics, and Biomedical Research
Innsbruck Medical University
2012-2024
Universität Innsbruck
2016-2024
University of Bern
2004
Bulgarian Academy of Sciences
1999
The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1-3. Methods based on conformation capture have mapped structures in neuronal systems such as vitro differentiated neurons, neurons isolated through fluorescence-activated sorting from cortical tissues pooled different animals dissociated whole hippocampi4-6. However, changes organization captured by imaging, the relocation Bdnf away nuclear periphery after activation7, are...
The DNA-binding protein SATB2 is genetically linked to human intelligence. We studied its influence on the three-dimensional (3D) epigenome by mapping chromatin interactions and accessibility in control versus SATB2-deficient cortical neurons. find that affects looping between enhancers promoters of neuronal-activity-regulated genes, thus influencing their expression. It also alters A/B compartments, topologically associating domains, frequently interacting regions. Genes SATB2-dependent 3D...
SATB2 is a risk locus for schizophrenia and encodes DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 almost exclusively expressed in pyramidal neurons of two regions important memory formation, cerebral cortex CA1-hippocampal field. Here we show required key hippocampal functions since deletion from mouse forebrain prevents stabilization synaptic long-term potentiation markedly impairs fear object discrimination memory. At molecular level,...
Dehydroepiandrosterone (DHEA) exerts beneficial effects on blood glucose levels and insulin sensitivity in obese rodents humans, resembling the of peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands opposing those glucocorticoids; however, underlying mechanisms remain unclear. Glucocorticoids are reactivated locally by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which is currently considered as a promising target for treatment obesity diabetes. Using...
Protein-coding genes, guiding differentiation of ES cells into neural cells, have extensively been studied in the past. However, for class ncRNAs only involvement some specific microRNAs (miRNAs) has described. Thus, to characterize entire small non-coding RNA (ncRNA) transcriptome, involved mouse we generated three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i.e. from pluripotent progenitors and differentiated respectively. By high-throughput sequencing...
SATB2 is associated with schizophrenia and an important transcription factor regulating neocortical organization circuitry. Rare mutations in cause a syndrome that includes developmental delay, mouse studies identify role for learning memory. Interacting partners BCL11B GATAD2A are also risk genes indicating other interacting or regulated by making contribution to cognition. We used data from Satb2 models generate three gene-sets contain either functionally related targeted at different...
The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report the removal special AT-rich binding protein 2 (SATB2), a nuclear known to bind matrix attachment regions, is event initiating myogenic differentiation. deletion myoblast SATB2 vitro initiates remodeling and accelerates differentiation, which dependent on caspase 7-mediated...
During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In adult CNS, pyramidal neurons of all a regulator synaptic plasticity long-term memory. Common variation locus confers risk schizophrenia, whereas rare, de novo structural single nucleotide variants cause severe intellectual disability absent or limited speech. To characterize differences molecular function developing vs neocortex, we isolated interactomes...
SATB2 is a schizophrenia risk gene and genetically associated with human intelligence. How it affects cognition at molecular level currently unknown. Here, we show that interactions between SATB2, chromosomal scaffolding protein, the inner nuclear membrane protein LEMD2 orchestrate response of pyramidal neurons to neuronal activation. Exposure novel environment in vivo causes changes shape CA1 hippocampal via SATB2-dependent mechanism. The activity-driven plasticity envelope requires not...
Sympathetic neurons can switch their neurotransmitter phenotype from noradrenergic to cholinergic on exposure neuropoietic cytokines in vitro and vivo . Here, we provide evidence that this transspecification is regulated by the chromatin architecture protein Satb2. Treatment with ciliary neurotrophic factor (CNTF) leukemia inhibitory rapidly strongly increases Satb2 transcript levels cultures of rat superior cervical ganglia neurons. Knockdown endogenous short interfering RNA prevents...
Although the p38 mitogen-activated protein kinases are active in many neuronal populations peripheral and central nervous systems, little is known about physiological functions of postmitotic neurons. We report that activity determines vitro vivo switch from noradrenergic to cholinergic neurotransmission occurs sympathetic neurons on exposure neuropoietic cytokines CNTF LIF. This transdifferentiation serves as a model for plastic mechanisms enable mature change some their without passing...
Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate completely lose their previous PNS characteristics and acquire identity of neural derived spinal cord. Reprogramming proceeds rapidly results a homogenous population Olig2-, Sox3-, Lex-positive CNS cells. Low-level...
Abstract Objective: In Friedreich’s ataxia (FRDA), the most affected tissues are not accessible to sampling and available transcriptomic findings originate from blood-derived cells animal models. Herein, we aimed at dissecting for first time pathophysiology of FRDA by means RNA-sequencing in an tissue sampled vivo. Methods: Skeletal muscle biopsies were collected seven patients before after treatment with recombinant human Erythropoietin (rhuEPO) within a clinical trial. Total RNA...
Abstract Neurons and oligodendrocytes are terminally differentiated cells that sustain cascades of gene activation repression to execute highly specialized functions, while retaining homeostatic control. To study long-range chromatin folding without disturbing the native tissue environment, we developed Genome Architecture Mapping in combination with immunoselection (immunoGAM), applied it three cell types from adult murine brain: dopaminergic neurons (DNs) midbrain, pyramidal glutamatergic...
Satb2 is a DNA binding protein that specifically binds nuclear matrix attachment region and functions as regulator of the transcription large chromatin domains. Unlike its well addressed role during brain development, in adult under-investigated. It has been shown deletion from forebrain mice significantly impaired long term memory for contextual fear object recognition memory. The aim present study was to investigate effects appetitive stimuli such cocaine social interaction expression rat...
Summary Induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report removal special AT-rich binding protein 2 (SATB2), a nuclear binds matrix attachment regions, is event initiating myogenic differentiation. Deletion SATB2 muscle cell culture models and vivo, accelerates differentiation depletes the progenitor pool, respectively. Genome...
Vertebrate sympathetic neurons have the remarkable potential to switch their neurotransmitter phenotype from noradrenergic cholinergic—a phenomenon that has been intensively studied in rat and chicken models. In both species, loss of markers concomitant upregulation cholinergic occurs response neuropoietic cytokines such as ciliary neurotrophic factor (CNTF). However, other aspects including developmental timing, target tissues neurons, dependence on factors differ between two species. Here...