A5058519318- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Virus-based gene therapy research
- Fungal and yeast genetics research
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- Histone Deacetylase Inhibitors Research
- Viral Infectious Diseases and Gene Expression in Insects
- Pancreatic and Hepatic Oncology Research
- Neuroblastoma Research and Treatments
- Chromatin Remodeling and Cancer
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Glycosylation and Glycoproteins Research
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
University of Freiburg
2017-2025
University Medical Center Freiburg
2017-2025
German Cancer Research Center
2017-2024
Heidelberg University
2019-2024
Deutschen Konsortium für Translationale Krebsforschung
2019-2024
University Medical Center Utrecht
2009-2019
Utrecht University
2005-2019
German Marine Research Consortium
2019
Vanderbilt University
2014
Cancer Genetics (United States)
2014
Methylation of lysine 4 on histone H3 (H3K4) at promoters is tightly linked to transcriptional regulation in human cells. At least six different COMPASS-like multisubunit (SET1/MLL) complexes that contain methyltransferase activity for H3K4 have been described, but a comprehensive and quantitative analysis these SET1/MLL lacking. We applied label-free mass spectrometry determine the subunit composition stoichiometry complexes. identified both known novel, unique shared interactors determined...
Abstract Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order overcome silencing of genes and enable transcription from genome. In humans, ZGA induced by DUX4, a pioneer factor that drives expression downstream germline-specific retroelements. Here we show herpesviruses all subfamilies, papillomaviruses Merkel cell polyomavirus actively induce DUX4 promote viral replication. Analysis single-cell sequencing data sets patients shows...
The carbon catabolite repressor protein 4 (Ccr4)–Negative on TATA (Not) complex controls gene expression at two levels. In the nucleus, it regulates basal transcription machinery, nuclear receptor-mediated and histone modifications. cytoplasm, is required for messenger RNA (mRNA) turnover through its associated deadenylases, Ccr4 Caf1. Not1 largest of Ccr4–Not serves as a scaffold other subunits complex. Here, we provide evidence that human in cytoplasm associates with C-terminal domain...
Abstract The product of the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor gene, menin, is an integral component MLL1/MLL2 histone methyltransferase complexes specific for Lys4 H3 (H3K4). We show that menin a transcriptional coactivator nuclear receptors estrogen and vitamin D. Activation endogenous estrogen-responsive TFF1 (pS2) gene results in promoter recruitment elevated trimethylation H3K4. Knockdown reduces both activated transcription H3K4 trimethylation. In addition, can...
The Ccr4-Not complex is evolutionarily conserved and important for regulation of mRNA synthesis decay. composition the yeast has been well described. Orthologues components have identified in human cells including multiple subunits with deadenylase activity. In present study, we examine an in-depth proteomic approach using stable cell lines expressing tagged CNOT proteins. We find at least four different variants complex, consisting seven core proteins mutually exclusive associated subunits....
Article18 August 2009Open Access A comprehensive framework of E2–RING E3 interactions the human ubiquitin–proteasome system Sjoerd J L van Wijk Division Biomedical Genetics, Department Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, The Netherlands Search for more papers by this author de Vries NMR Spectroscopy, Bijvoet Biomolecular Research, Utrecht University, Patrick Kemmeren Anding Huang Rolf Boelens Alexandre M Bonvin H Th Marc Timmers Corresponding...
The functional organization of eukaryotic genomes correlates with specific patterns histone methylations. Regulatory regions in such as enhancers and promoters differ their extent methylation H3 at lysine-4 (H3K4), but it is largely unknown how the different states are specified controlled. Here, we show that Kdm5c/Jarid1c/SMCX member Kdm5 family H3K4 demethylases can be recruited to both enhancer promoter elements mouse embryonic stem cells neuronal progenitor cells. Knockdown Kdm5c...
Abstract Cells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling a multisubunit complex are dispersed the genome of eukaryotes, it is unclear how these protein complexes assemble. Here, we show that mammalian nuclear transcription (TFIID, TREX-2 and SAGA) composed large number subunits, but lacking precise architectural details built co-translationally. We demonstrate...
TFIIH is a multisubunit protein complex involved in RNA polymerase II transcription and nucleotide excision repair, which removes wide variety of DNA lesions including UV-induced photoproducts. Mutations the DNA-dependent ATPase/helicase subunits TFIIH, XPB XPD, are associated with three inherited syndromes as follows: xeroderma pigmentosum or without Cockayne syndrome trichothiodystrophy. By using epitope-tagged XPD we purified mammalian carrying wild type an active-site mutant subunit....
Using a protein binding assay, we show that the amino-terminal 204 amino acids of c-Myc interact directly with key component basal transcription factor TFIID, TATA box-binding (TBP). Essentially same region also binds product retinoblastoma gene, RB protein. coimmunoprecipitates TBP in lysates mammalian cells, demonstrating proteins are complexed vivo. A short peptide spans site E7 human papilloma virus type 16 interferes to TBP. The blocks adenovirus E1A TBP, suggesting and bind through...
The TFIID activity recognizes a TATA-box element and supports formation of an initiation complex containing RNA polymerase II. Antisera specific for the 38-kD human protein were used to determine whether this cofractionated with activity. Surprisingly, in HeLa whole-cell extracts was resolved into two different size complexes, one 300 kD greater than 700 kD. Cofractionation studies suggest that both complexes contain protein; thus, component large is probably responsible recognition TATA...