A5030515369- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Histone Deacetylase Inhibitors Research
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Hematopoietic Stem Cell Transplantation
- Chronic Myeloid Leukemia Treatments
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- Acute Lymphoblastic Leukemia research
- Pluripotent Stem Cells Research
- DNA and Nucleic Acid Chemistry
- Cancer-related gene regulation
- interferon and immune responses
- Genetics and Neurodevelopmental Disorders
- Nuclear Receptors and Signaling
- Chronic Lymphocytic Leukemia Research
- Cytomegalovirus and herpesvirus research
- Cancer Cells and Metastasis
- Chromatin Remodeling and Cancer
University Medical Center Groningen
2012-2024
University of Groningen
2007-2024
Dialyse Centrum Groningen
2017
Erasmus University Rotterdam
2000-2002
Erasmus MC
2002
University Medical Center Utrecht
2001
Utrecht University
2000
The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled (TCR). patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB DNA-dependent ATPase of the SWI2/SNF2 family. SWI2/SNF2-like proteins are implicated chromatin remodeling during transcription. Since structure also affects efficiency, activities within expected. Here we used purified recombinant investigate whether it can remodel...
Highlights•The non-canonical PRC1.1 complex is critically important for human LSCs•Several members are overexpressed in primary AML•PRC1.1 can bind TSSs the absence of repressive H3K27me3 PRC2 mark•PRC1.1 targets actively transcribed genes involved metabolismSummaryPolycomb proteins classical regulators stem cell self-renewal and lineage commitment frequently deregulated cancer. Here, we find that complex, as identified by mass-spectrometry-based proteomics, leukemic cells. Downmodulation...
The Cockayne syndrome B (CSB) protein is essential for transcription-coupled DNA repair (TCR), which dependent on RNA polymerase II elongation. TCR required to quickly remove the cytotoxic transcription-blocking lesions. Functional GFP-tagged CSB, expressed at physiological levels, was homogeneously dispersed throughout nucleoplasm in addition bright nuclear foci and nucleolar accumulation. Photobleaching studies showed that GFP-CSB, as part of a high molecular weight complex, transiently...
Maintenance of epigenetic modifiers is utmost importance to preserve the epigenome and consequently appropriate cellular functioning. Here, we analyzed Polycomb group protein (PcG) complex integrity in response heat shock (HS). Upon HS, various Repressive Complex (PRC)1 PRC2 subunits, including CBX proteins, but also other chromatin regulators, are found accumulate nucleolus. In parallel, binding PRC1/2 target genes strongly reduced, coinciding with a dramatic loss H2AK119ub H3K27me3 marks....
Embryonic stem (ES) cells are able to grow indefinitely (self-renewal) and have the potential differentiate into all adult cell types (pluripotency). The regulatory network that controls pluripotency is well characterized, whereas molecular basis for transition from self-renewal differentiation of ES much less understood, although dynamic epigenetic gene silencing chromatin compaction clearly implicated. In this study, we report UTF1 (undifferentiated embryonic transcription factor 1)...
In an attempt to unravel functionality of the non-canonical PRC1.1 Polycomb complex in human leukemogenesis, we show that USP7 and TRIM27 are integral components PRC1.1. interactome analyses is predominant co-precipitating with USP7. inhibition results disassembly loss chromatin binding, coinciding reduced H2AK119ub H3K27ac levels diminished gene transcription active PRC1.1-controlled loci, whereas marks also lost at PRC1 loci. reciprocally required for incorporation into PRC1.1, knockdown...
Abstract Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin—properties are important for ES cell pluripotency differentiation. Here, we demonstrate a role undifferentiated transcription factor 1 (UTF1) in regulating chromatin structure. Using immunoprecipitation-on-chip analysis, identified >1,700 UTF1 target genes significantly overlap with previously Nanog, Oct4, Klf-4, c-Myc, Rex1 targets. Gene expression profiling knock...
Endoplasmic reticulum–synthesized membrane proteins traffic through the nuclear pore complex (NPC) en route to inner (INM). Although many pass NPC by simple diffusion, two yeast proteins, ScSrc1/ScHeh1 and ScHeh2, are actively imported. In these a localization signal (NLS) an intrinsically disordered linker encode sorting for recruiting transport factors FG-Nup RanGTP-dependent NPC. Here we address whether similar import mechanism applies in metazoans. We show that (putative) NLSs of...
The human RNA polymerase II transcription factor B-TFIID consists of TATA-binding protein (TBP) and the TBP-associated (TAF) TAFII170 can rapidly redistribute over promoter DNA. Here we report identification TBP-binding regions in TAFII170. We have defined TBP interaction domain within three amino-terminal regions: residues 2 to 137, 290 381, 380 460. Each region contains a pair Huntington-elongation-A subunit-Tor repeats exhibits species-specific interactions with family members....
Leukemic stem cells (LSCs) reside within bone marrow niches that maintain their relatively quiescent state and convey resistance to conventional treatment. Many of the microenvironmental signals converge on RAC GTPases. Although it has become clear proteins fulfill important roles in hematopoietic compartment, little been revealed about downstream effectors molecular mechanisms. We observed BCR-ABL-transduced human stem/progenitor (HSPCs) depletion RAC2 but not RAC1 induced a marked...
Acute myeloid leukemia (AML) remains challenging to treat, which in part relates genetic heterogeneity of the disease, protective tumor microenvironment driving resistance therapy, and also immune evasion characteristics leukemic cells. Targeting epigenetic programs AML provides an attractive opportunity impair long-term proliferation induce differentiation. The novel inhibitor JNJ- 75276617 (bleximenib) targets menin-KMT2A interaction preclinical efficacy (Kwon et al1). Here, we provide...
The TATA-binding protein (TBP) plays a central role in eukaryotic transcription and forms complexes with TBP-associated factors (TAFs). genes encoding TAFII proteins frequently map to chromosomal regions altered human neoplasias. TAFII170 of B-TFIID is member the SF2 superfamily putative helicases. Members this have also been implicated several genetic disorders. In study we isolated genomic clones show that gene contains 37 introns. Ribonuclease-protection experiments revealed has multiple...
ABSTRACT Acute myeloid leukemia (AML) is a highly heterogeneous disease in which genetic and epigenetic changes disturb regulatory mechanisms controlling stem cell fate maintenance. AML still remains difficult to treat, particular poor risk patients carrying TP53 mutations. Here, we identify the deubiquitinase USP7 as an integral member of non-canonical PRC1.1 show that targeting provides alternative therapeutic approach for AML. inhibitors effectively induced apoptosis (primary) cells, also...