A5023008698- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Chromatin Remodeling and Cancer
- RNA modifications and cancer
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Congenital heart defects research
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Neurogenesis and neuroplasticity mechanisms
- DNA Repair Mechanisms
- Ocular Disorders and Treatments
- Autism Spectrum Disorder Research
- Hepatitis C virus research
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Genomic variations and chromosomal abnormalities
- Hepatitis Viruses Studies and Epidemiology
- Nuclear Structure and Function
- Mitochondrial Function and Pathology
Erasmus University Rotterdam
2012-2025
Erasmus MC
2015-2025
European Molecular Biology Laboratory
2007
Marie Curie
2000-2004
Western General Hospital
2000
Leiden University
1996-1998
Polycomb-repressive complex 1 (PRC1) has a central role in the regulation of heritable gene silencing during differentiation and development. PRC1 recruitment is generally attributed to interaction chromodomain core protein Polycomb with trimethyl histone H3K27 (H3K27me3), catalyzed by second complex, PRC2. Unexpectedly we find that RING1B, catalytic subunit PRC1, associated monoubiquitylation H2A are targeted closely overlapping sites wild-type PRC2-deficient mouse embryonic stem cells...
Transcription factors, such as Oct4, are critical for establishing and maintaining pluripotent cell identity. Whereas the genomic locations of several pluripotency transcription factors have been reported, spectrum their interaction partners is underexplored. Here, we use an improved affinity protocol to purify Oct4-interacting proteins from mouse embryonic stem cells (ESCs). Subsequent purification Oct4 Sall4, Tcfcp2l1, Dax1, Esrrb resulted in interactome 166 proteins, including...
Embryonic stem (ES) cell self-renewal is regulated by transcription factors, including Oct4, Sox2, and Nanog. A number of additional transcriptional regulators ES have recently been identified, the orphan nuclear receptor estrogen-related beta (Esrrb). However, mode action Esrrb in cells unknown. Here, using an Oct4 affinity screen, we identify as partner protein. can interact with independently DNA. recruited near Oct-Sox element Nanog proximal promoter, where it positively regulates...
The locations of transcriptional enhancers and promoters were recently mapped in many mammalian cell types. Proteins that bind those regulatory regions can determine identity but have not been systematically identified. Here we purify native enhancers, or heterochromatin from embryonic stem cells by chromatin immunoprecipitations (ChIP) for characteristic histone modifications identify associated proteins using mass spectrometry (MS). 239 factors are identified predicted to with different...
Abstract The Mediator complex regulates transcription by connecting enhancers to promoters. High binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of may explain its role in these processes but have not been identified comprehensively. Here, we purify from neural stem cells (NSCs) identify 75 protein-protein interaction partners. We NSCs show that Mediator-interacting chromatin modifiers colocalize with at enhancers. Transcription...
Polycomb group (PcG) proteins play an important role in the control of developmental gene expression higher organisms. In mammalian systems, PcG participate pluripotency, cell fate, cycle regulation, X chromosome inactivation and parental imprinting. this study we have analysed function mouse protein polycomblike 2 (Pcl2), one three homologues Drosophila Polycomblike (Pcl) protein. We show that Pcl2 is expressed at high levels during early embryogenesis embryonic stem (ES) cells. At...
SRY and other Sox-type transcription factors are important developmental regulators with various implications in human disease. In this study, we identified Exp4 (exportin 4) as an interaction partner of Sox2 mouse embryonic stem cells neural progenitors. We show that, besides its established function nuclear export, acts a bona fide import receptor for SRY. Thus, is example transport carrying distinct cargoes into different directions. contrast to published observed that the activity Imp-α...
Mutations in the gene encoding methyl-CpG-binding protein MECP2 are major cause of Rett syndrome, an autism spectrum disorder mainly affecting young females. MeCP2 is abundant chromatin-associated protein, but how and when its absence begins to alter brain function still far from clear. Using a stem cell-based system allowing synchronous differentiation neuronal progenitors, we found that MeCP2, size nuclei fails increase at normal rates during differentiation. This accompanied by marked...
The chromosomal protein SMCHD1 plays an important role in epigenetic silencing at diverse loci, including the inactive X chromosome, imprinted genes, and facioscapulohumeral muscular dystrophy locus. Although homology with canonical SMC family proteins suggests a chromosome organization, mechanisms underlying function target site selection remain poorly understood. Here we show that forms active GHKL-ATPase homodimer, contrasting complexes, which exist as tripartite ring structures. Electron...
Xist is indispensable for X chromosome inactivation. However, how RNA directs chromosome-wide silencing and why some regions are more efficiently silenced than others remains unknown. Here, we explore the function of by inducing ectopic expression from multiple different X-linked autosomal loci in mouse aneuploid female diploid embryonic stem cells which Xist-mediated does not lead to lethal functional monosomy. We show that faithfully recapitulates endogenous inactivation any location on...
The size of the human head is highly heritable, but genetic drivers its variation within general population remain unmapped. We perform a genome-wide association study on (N = 80,890) and identify 67 loci, which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, most have widespread effects. Gene set enrichment observed for various cancers p53, Wnt, ErbB signaling pathways. Genes harboring lead enriched macrocephaly syndrome genes (37-fold) high-fidelity...
Chromatin compaction of deoxyribonucleic acid (DNA) presents a major challenge to the detection and removal DNA damage. Helix-distorting lesions that block transcription are specifically repaired by transcription-coupled nucleotide excision repair, which is initiated binding CSB protein lesion-stalled RNA polymerase II. Using live cell imaging, we identify novel function for two distinct mammalian ISWI adenosine triphosphate (ATP)-dependent chromatin remodeling complexes in resolving...
FOXP transcription factors play important roles in neurodevelopment, but little is known about how their transcriptional activity regulated. proteins cooperatively regulate gene expression by forming homo- and hetero-dimers with each other. Physical associations other might also modulate the functions of proteins. However, few FOXP-interacting have been identified so far. Therefore, we sought to discover additional that interact brain-expressed proteins, FOXP1, FOXP2 FOXP4, through...
Abstract IFN-α has been used for decades to treat chronic hepatitis B and C as an off-label treatment some cases of E virus (HEV) infection. TNF-α is another important cytokine involved in inflammatory disease, which can interact with interferon signaling. Because interferon-stimulated genes (ISGs) are the ultimate antiviral effectors signaling, this study aimed understand regulation ISG transcription activity by TNF-α. In study, inhibited replication HCV 71 ± 2.4% HEV 41 4.9%....
Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one most common human developmental disorders. Despite decades phenotype-driven research, 80-90% aneuploidy-negative individuals with a probable genetic aetiology do not have diagnosis. Here we report associated variants in two X-linked cohesin complex genes, STAG2 and SMC1A, loss-of-function 10 missense variant one. Additionally, four genes that are X-linked, SMC3 RAD21. Using whole mount situ hybridization, show...