A5039349041- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Erythrocyte Function and Pathophysiology
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- RNA Research and Splicing
- Iron Metabolism and Disorders
- RNA and protein synthesis mechanisms
- Zebrafish Biomedical Research Applications
- Biotin and Related Studies
- Prenatal Screening and Diagnostics
- Animal Genetics and Reproduction
- Click Chemistry and Applications
- Blood groups and transfusion
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- Complement system in diseases
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Williams Syndrome Research
- Parvovirus B19 Infection Studies
King's College London
2019-2025
London Cancer
2023
FORTH Institute of Molecular Biology and Biotechnology
2003-2019
Foundation for Research and Technology Hellas
2013-2018
Alexander Fleming Biomedical Sciences Research Center
2008-2016
Molecular Oncology (United States)
2015
University of Florida
2014
University of Crete
2003-2013
Erasmus MC
2004-2011
Erasmus University Rotterdam
2002-2009
Proteomic approaches require simple and efficient protein purification methodologies that are amenable to high throughput. Biotinylation is an attractive approach for complex due the very affinity of avidin/streptavidin biotinylated templates. Here, we describe single-step transcription factor complex(es) based on specific in vivo biotinylation. We expressed bacterial BirA biotin ligase mammalian cells demonstrated biotinylation a hematopoietic bearing small (23-aa) artificial peptide tag....
SummaryTranscriptional heterogeneity within embryonic stem cell (ESC) populations has been suggested as a mechanism by which seemingly homogeneous population can initiate differentiation into an array of different types. Chromatin remodeling proteins have shown to control transcriptional variability in yeast and be important for mammalian ESC lineage commitment. Here we show that the Nucleosome Remodeling Deacetylation (NuRD) complex, is required commitment, modulates both dynamic range set...
Ring1B/Rnf2 is a RING finger protein member of the Polycomb group (PcG) proteins, which form chromatin-modifying complexes essential for embryonic development and stem cell renewal are commonly deregulated in cancer. ubiquitin E3 ligase that catalyzes monoubiquitylation histone H2A, one modifications needed transcriptional repression activity PcG proteins. was shown to be part two complexes, PRC1 complex E2F6.com-1 complex, also contains non-PcG members, thus raising prospect additional...
We have used a linker-based ligation strategy to combine two 35-kb cosmid inserts from the human beta-globin locus into one linear fragment containing entire locus. This 70-kb was introduced transgenic mice by microinjection of fertilized eggs. Southern blot analysis showed that single complete transgene can be germ line with high efficiency. Analysis expression patterns during development shows epsilon-globin gene behaves as purely embryonic gene, gamma-globin an and early fetal adult gene....
The human β-globin locus control region (LCR) is required for the maintenance of an open chromatin configuration locus. It interacts with genes and hypersensitive regions flanking to form active hub (ACH) transcribing genes. Proper developmental globin largely determined by gene proximal regulatory sequences. Here, we provide first functional evidence role most sites LCR promoter in ACH. When deleted context a full LCR, ACH maintained remaining proximity. Additional deletion site HS3 or HS2...
Lineage specification and cellular maturation require coordinated regulation of gene expression programs. In large part, this is dependent on the activator repressor functions protein complexes associated with tissue-specific transcriptional regulators. study, we have used a proteomic approach to characterize multiprotein containing key hematopoietic regulator SCL in erythroid megakaryocytic cell lines. One novel SCL-interacting proteins identified both types corepressor ETO-2. Interaction...
Ldb1, a ubiquitously expressed LIM domain binding protein, is essential in number of tissues during development. It interacts with Gata1, Tal1, E2A and Lmo2 to form transcription factor complex regulating late erythroid genes. We identify novel Ldb1 interacting proteins erythroleukaemic cells, particular the repressor protein Eto-2 (and its family member Mtgr1), cyclin-dependent kinase Cdk9, bridging Lmo4. MO-mediated knockdowns zebrafish show these factors be for definitive haematopoiesis....
Nuclear receptors TR2 and TR4 (TR2/TR4) were previously shown to bind in vitro direct repeat elements the mouse human embryonic fetal β-type globin gene promoters play critical roles silencing of these genes. By chromatin immunoprecipitation (ChIP) we show that, adult erythroid cells, TR2/TR4 but not β-globin promoter. We purified protein complexes containing biotin-tagged from cells identified DNMT1, NuRD, LSD1/CoREST repressor complexes, as well HDAC3 TIF1β, all known confer epigenetic...
Vivax malaria has long been thought to be absent from sub-Saharan Africa owing the high proportion of individuals lacking Duffy antigen receptor for chemokines (DARC) in their erythrocytes. The interaction between P. vivax Duffy-binding protein (PvDBP) and DARC is assumed main pathway used by merozoites invade reticulocytes. However, increasing number reports cases genotypically Duffy-negative (DN) raised questions regarding invasion pathway(s). Here, we show that a subset DN erythroblasts...
The clinical severity of sickle cell disease (SCD) is strongly influenced by the level fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted genome-wide association study for levels 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed replication meta-analysis exercise four independent cohorts (3,582 patients). To dissect signals at loci, we performed...
Friend of GATA1 (FOG-1) is an essential transcriptional co-factor the master erythroid transcription factor GATA1. The knockout Zfpm1 gene, coding for FOG-1, results in early embryonic lethality due to anemia mice, similar lethal phenotype Gata1 gene knockout. However, a detailed molecular analysis erythropoiesis presently incomplete. To this end, we used CRISPR/Cas9 mouse erythroleukemic (MEL) cells. Phenotypic characterization DMSO-induced terminal differentiation showed that MEL cells did...