A5039728153- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- RNA modifications and cancer
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Advanced Proteomics Techniques and Applications
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Genomics and Phylogenetic Studies
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Glioma Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Microtubule and mitosis dynamics
- Cell death mechanisms and regulation
- Genetics and Neurodevelopmental Disorders
- Enzyme Structure and Function
- Nuclear Structure and Function
- Metabolomics and Mass Spectrometry Studies
- Neuroblastoma Research and Treatments
- Bioinformatics and Genomic Networks
- Pluripotent Stem Cells Research
Institute of Molecular Biology
2021-2024
Johannes Gutenberg University Mainz
2021
Oncode Institute
2019
Radboud University Nijmegen
2014-2019
Radboud Institute for Molecular Life Sciences
2014-2019
Radboud University Medical Center
2014-2019
Erasmus MC
2015
Cancer Genomics Centre
2014
University Medical Center Utrecht
2013-2014
Utrecht University
2014
Abstract PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types DNA lesions. PARP inhibitors are used for the treatment BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss replication fork protection is proposed as one mechanism that contributes vulnerability cells inhibitors. However, mechanisms regulate activity at stressed forks remain poorly understood. Here, we performed proximity proteomics isolation map putative regulators. We identified...
Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate reactivation after mitotic gene silencing. However, the loss of individual TFs often leads deregulation only a small proportion their targets, raising doubts on biological significance importance function. Here we used targeted proteomics TF ESRRB, an orphan nuclear receptor, discover large redundancy in binding among members protein super-family receptors. Focusing receptor NR5A2, which together with...
MBD5 and MBD6 are two members of the methyl-CpG-binding domain (MBD) family proteins that poorly characterized. Studies performed thus far have failed to show binding MBD methylated DNA. Here, we both interact with mammalian PR-DUB Polycomb protein complex in a mutually exclusive manner. Strikingly, is necessary sufficient mediate this interaction. Chromatin immunoprecipitation analyses reveal FOXK2/PR-DUB share subset genomic target genes, suggesting functional interaction vivo. Finally,...
Abstract How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components together maintain an erythroid-specific programme primed for activation until differentiation induced. A combination proteomics, functional genomics in vivo studies presented here...
Genetic mutations affecting chromatin modifiers are widespread in cancers. In malignant peripheral nerve sheath tumors (MPNSTs), Polycomb repressive complex 2 (PRC2), which plays a crucial role gene silencing, is inactivated through recurrent core subunits embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), but PRC2’s main catalytic subunit enhancer (EZH2) have never been found. This contrast to myeloid lymphoid malignancies, harbor frequent loss-of-function...
Abstract To clarify whether differential compartmentalization of Survivin impacts temozolomide (TMZ)-triggered end points, we established a well-defined glioblastoma cell model in vitro (LN229 and A172) vivo, distinguishing between its nuclear cytoplasmic localization. Expression export sequence (NES)-mutated (SurvNESmut-GFP) led to impaired colony formation upon TMZ. This was not due enhanced death but rather increased senescence. Nuclear-trapped reduced homologous recombination...
Abstract Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual TFs often leads deregulation only a small proportion their mitotic targets, raising doubts on significance importance function. Here, we used targeted proteomics TF ESRRB, an orphan nuclear receptor, discover unexpected redundancy among members protein superfamily receptors. Focusing receptor NR5A2, which together with ES-RRB is...
ABSTRACT The Polycomb machinery is required for the proper orchestration of gene expression by virtue its critical role in maintaining transcriptional silencing. It composed several chromatin modifying complexes, including Repressive Complex 2 (PRC2), which deposits H3K27me2/3. Here, we report identification a new cofactor PRC2, EZHIP (EZH1/2 Inhibitory Protein), expressed predominantly gonads. limits enzymatic activity PRC2 and lessens interaction between core complex accessory subunits,...