A5056298302- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Nuclear Structure and Function
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Estrogen and related hormone effects
- Renal and related cancers
- Cancer-related molecular mechanisms research
- Polyomavirus and related diseases
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Amyotrophic Lateral Sclerosis Research
- Cytomegalovirus and herpesvirus research
- Circular RNAs in diseases
- Endoplasmic Reticulum Stress and Disease
- Genomic variations and chromosomal abnormalities
- Invertebrate Immune Response Mechanisms
FORTH Institute of Molecular Biology and Biotechnology
2013-2017
Foundation for Research and Technology Hellas
2008-2016
Czech Academy of Sciences
2014
Leibniz Institute of Virology (LIV)
2000-2005
Sabin Vaccine Institute
2005
Helmholtz Centre for Infection Research
2004
Witten/Herdecke University
2004
Universität Hamburg
2002
University of Konstanz
1992-2001
Methylation of arginine residues is a widespread post-translational modification proteins catalyzed by small family protein methyltransferases (PRMTs). Functionally, the appears to regulate functions and interactions that affect gene regulation, signalling subcellular localization nucleic acids. All members have been, different degrees, characterized individually their implication in cellular processes has been inferred from characterizing substrates interactions. Here, we report first...
Polyglutamine expansion in androgen receptor (AR) is responsible for spinobulbar muscular atrophy (SBMA) that leads to selective loss of lower motor neurons. Using SBMA as a model, we explored the relationship between protein structure/function and neurodegeneration polyglutamine diseases. We show here arginine methyltransferase 6 (PRMT6) specific co-activator normal mutant AR interaction PRMT6 with significantly enhanced mutant. occurs through steroid motif, LXXLL, activating function 2...
SARs (scaffold attachment regions) are candidate DNA elements for partitioning eukaryotic genomes into independent chromatin loops by attaching to proteins of a nuclear scaffold or matrix. The interaction with the is evolutionarily conserved and appears be due specific binding that recognize mechanism not yet understood. We describe novel, protein domain specifically binds but related SAR motifs other proteins. This was first identified in human factor A (SAF-A) thus designated SAF-Box....
We show that SAF‐A, a nuclear protein which specifically binds vertebrate scaffold‐attachmentregion (SAR) elements with high affinity is identical hnRNP‐U, assumed to be involved in packaging of hnRNA ribonucleoprotein particles. Ultraviolet cross‐linking experiments the protein, referred as hnRNP‐U/SAF‐A, bound chromosomal DNA vivo. In vitro , isolated double‐stranded and single‐stranded forms higher ordered nucleic‐acid–protein complexes. Filter‐binding performed different types natural...
The activation of mammalian origins replication depends so far on ill understood epigenetic events, such as binding transcription factors, chromatin structure, and nuclear localization. Understanding these mechanisms is not only a scientific challenge but also represents prerequisite for the rational design nonviral episomal vectors cells. In this paper, we demonstrate that tetramer 155-bp minimal scaffold/matrix attached region DNA module linked to an upstream unit sufficient mitotic...
We have purified to near homogeneity a novel nuclear protein from HeLa cells, that specifically binds scaffold or matrix attachment region DNA elements (S/MAR DNA). The protein, designated SAF-B for factor B, is an abundant component of chromatin, but not the and expressed in all human tissues investigated. Antibodies against were raised rabbit used isolate complete cDNA encoding by immunoscreening. As predicted sequence, contains 849 amino acids (96 696 Da), without significant homology any...
Amyotrophic lateral sclerosis (ALS) is a late onset and progressive motor neuron disease. Mutations in the gene coding for fused sarcoma/translocated liposarcoma (FUS) are responsible some cases of both familial sporadic forms ALS. The mechanism through which mutations FUS result degeneration loss not known. belongs to family TET proteins, regulated at post-translational level by arginine methylation. Here, we investigated impact methylation pathogenesis FUS-related We found that wild type...
Recent data revealed that DEK associates with splicing complexes through interactions mediated by serine/arginine-repeat proteins. However, the protein has also been shown to change topology of DNA in chromatin vitro. This could indicate resides on cellular chromatin. To investigate vivo localization DEK, we performed cell fractionation studies, immunolabeling, and micrococcal nuclease digestion analysis. Most was found be released DNase treatment nuclei, only a small amount RNase....
Arginine methylation is a posttranslational protein modification catalyzed by family of arginine methyltransferases (PRMT), the predominant member which PRMT1. Despite its major role in nuclear proteins, surprisingly little known about subcellular localization and dynamics We show here that only fraction PRMT1 located nucleus, but predominantly cytoplasmic. Fluorescence recovery after photobleaching experiments reveal highly mobile both cytoplasm nucleus. However, inhibition leads to...
The protein heterogeneous nuclear ribonucleoprotein U (hnRNP-U, also known as scaffold attachment factor A, SAF-A) is an abundant component of hnRNP particles and the matrix. Previous experiments have demonstrated that, in vitro, hnRNP-U specifically binds to scaffold/matrix (S/MAR) region DNA elements could thus be involved higher order chromatin structure. In this paper we report on use chemical cross-linking investigate whether bound vivo, which a prerequisite for its presumed function...
The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that able to modulate gene activity by binding its response element, interacting with other factors, and contacting several accessory proteins such as coactivators. Here we show GRIP120, one of the factors have identified interact receptor, identical heterogeneous nuclear ribonucleoprotein U (hnRNP U), matrix protein RNA well scaffold attachment regions. GR·hnRNP complexes were blotting coimmunoprecipitation....
Components of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex and other nucleic acid-binding proteins are subject to methylation on specific arginine residues by catalytic activity methyltransferases. The has been implicated in transcriptional regulation RNA protein trafficking signal transduction, but mechanism which these functions achieved remained undetermined. We show here that predominant methyltransferase human cells, 1 (PRMT1), is associated with hnRNP complexes,...
Abstract Higher order chromatin organization in concert with epigenetic regulation is a key process that determines gene expression at the global level. The of dynamic domains and their associated protein factors intertwined nuclear function to create higher levels functional zones within cell nucleus. As step towards elucidating dynamics these zones, we have investigated spatial proximities among constellation functionally related sites are found euchromatic regions nucleus including: HP1γ,...
The scaffold attachment factor A (SAF-A; Romig et al., 1992), a human nuclear protein which specifically binds vertebrate SAR (scaffold attached region) DNA, is identical with hnRNP-U (Kiledjian & Dreyfuss, 1992). In this paper, we report on the purification of two forms that can be chromatographically separated. We show purified proteins represent isoforms, form 1 and 2 hnRNP-U, differ in their primary structure. Both isoforms bind to double- single-stranded DNA RNA. addition, they higher...
Methylation of arginine residues is a widespread post‐translational modification proteins catalyzed by family protein methyltransferases (PRMT), which PRMT1 the predominant member in human cells. We have previously described localization and mobility live cells, found that it shuttles between nucleus cytoplasm depending on methylation status substrate proteins. Recently, amino‐terminal splicing isoforms were shown to differ significantly intracellular localization, most interesting being...
Members of the caspase family cysteine proteases play essential roles in disintegration cellular architecture during apoptosis. Caspases have been grouped into subfamilies according to their preferred cleavage sites, with "apoptotic executioner" caspase-3 as prototype DE<i>X</i>D-dependent proteases. We show here that is more tolerant variations site than previously anticipated and present an example a noncanonical recognition efficiently cleaved by <i>in vitro</i> vivo</i>. The new was...
Transcriptional inactivation of one copy the X chromosome in female cells equalizes expression X-linked genes between males and females. This "dosage compensation" is a multistep process that involves epigenetic modifications chromatin induced by large non-coding RNA termed Xist. In contrast to protein-coding mRNA molecules, which are free diffuse roam entire nuclear interior, Xist locally constrained territory inactive chromosomes as yet unclear mechanisms. Recent results have suggested...