A5090741929- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Genomics and Chromatin Dynamics
- Hemoglobinopathies and Related Disorders
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- RNA Research and Splicing
- Genetic Syndromes and Imprinting
- Galectins and Cancer Biology
- Neonatal Health and Biochemistry
- Histiocytic Disorders and Treatments
- Iron Metabolism and Disorders
- RNA Interference and Gene Delivery
- Hemoglobin structure and function
- Trace Elements in Health
- RNA and protein synthesis mechanisms
- Bone and Joint Diseases
- Carbohydrate Chemistry and Synthesis
- Genetics and Neurodevelopmental Disorders
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Hematological disorders and diagnostics
- Kruppel-like factors research
European Molecular Biology Laboratory
2018-2025
Columbia University
2014-2017
École Normale Supérieure de Lyon
2006-2010
Centre National de la Recherche Scientifique
2007-2010
Université Claude Bernard Lyon 1
2010
Aarhus University
2008
Institut pour l'avancée des biosciences
2006-2007
Inserm
1978-2007
Hôpital Debrousse
2001
Centre Jean Bernard
1984
The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). mammalian Ogt gene X-linked, it essential for embryonic development the viability proliferating cells. We perturbed OGT’s function in vivo creating murine allelic series four amino acid substitutions, reducing catalytic activity to range degrees. severity lethality was proportional extent impairment catalysis, demonstrating that modification...
Previous studies have shown a marked effect of very high levels copper on red cell glucose-6-phosphate dehydrogenase and glutathione. When the more nearly physiological were studied, hexokinase, phosphofructokinase, phosphoglyceric kinase, pyruvate 6-phosphogluconate found to be inhibited. Inhibition was observed both when added directly hemolysates or prepared from cells whole blood which had been incubated with washed. The inhibition enzymes by completely reversed addition EDTA.
DNA methyltransferase 1 (DNMT1) is a multidomain protein believed to be involved only in the passive transmission of genomic methylation patterns via maintenance methylation. The mechanisms that regulate DNMT1 activity and targeting are complex poorly understood. We used embryonic stem (ES) cells investigate function uncharacterized bromo-adjacent homology (BAH) domains glycine–lysine (GK) repeats join regulatory catalytic DNMT1. removed BAH by means CRISPR/Cas9-mediated deletion within...
Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, paradoxically expressed at high levels differentiating neural progenitor cells. Using vitro vivo techniques modulate L1 expression, we report that play critical role human mouse brain development regulating...
The mechanisms by which methylated mammalian promoters are transcriptionally silenced even in the presence of all factors required for their expression have long been a major unresolved issue field epigenetics. Repression requires assembly methylation-dependent silencing complex that contains TRIM28 protein (also known as KAP1 and TIF1β), scaffolding without intrinsic repressive or DNA-binding properties. identity key effector within this represses transcription is unknown. We developed...
Abstract Background How reversible glycosylation of DNA-bound proteins acts on transcription remains scarcely understood. O-linked β-N-acetylglucosamine (O-GlcNAc) is the only known form modifying nuclear proteins, including RNA polymerase II (RNA Pol II) and many factors. Yet, regulatory function O-GlcNAc modification in mammalian chromatin unclear. Results Here, we combine genome-wide profiling O-GlcNAc-modified with perturbations intracellular glycosylation, II-degron, super-resolution...
Vertebrate heterochromatin contains a non-allelic variant of the histone H2A called macroH2A1, which has characteristic being three times size canonical H2A. The macroH2A1 C-terminal extension can recruit onto chromatin poly-ADP-ribose polymerase (PARP)1, is crucial for DNA repair. This led to speculation that could be essential genome surveillance; however, no experimental evidence supported this hypothesis. Because been found enriched on inactive X-chromosome in females, it thought play...
The vascular endothelial growth factor-A (VEGF) gene locus contains eight exons that span 14 kb. Alternative splicing generates multiple, different mRNAs in turn translate into at least five protein isoforms. While the canonical AUG start codon is located position 1039 exon 1, there also exists an upstream, in-frame CUG initiation drives expression of L-VEGF, containing additional 180 amino acids. Two separate internal ribosome entry sites (IRES) regulate activity each codon. Thus 5′-UTR...
THE BACKGROUND: Ribonuclease L (RNASEL), encoding the 2'-5'-oligoadenylate (2-5A)-dependent RNase L, is a key enzyme in interferon induced antiviral and anti-proliferate pathway. Mutations RNASEL segregate with disease prostate cancer families specific genotypes are associated an increased risk of cancer. Infection by human papillomavirus (HPV) major factor for uterine cervix subset head neck squamous cell carcinomas (HNSCC). HPV, Epstein Barr virus (EBV) sequences from mouse mammary tumor...
In this work we have studied the properties of novel mouse histone variant H2AL2. H2AL2 was used to reconstitute nucleosomes and structural functional these particles were by a combination biochemical approaches, atomic force microscopy (AFM) electron cryo-microscopy. DNase I hydroxyl radical footprinting as well micrococcal exonuclease III digestion demonstrated an altered structure all over nucleosomal DNA length. Restriction nuclease accessibility experiments revealed that interactions...
We have studied the functional and structural properties of nucleosomes reconstituted with H2BFWT, a recently identified putative histone variant H2B family totally unknown function. show that H2BFWT can replace conventional in nucleosome. The presence did not affect overall structure nucleosome, exhibited same stability as nucleosomes. SWI/SNF was able to efficiently remodel mobilize Importantly, contrast H2B, unable recruit chromosome condensation factors participate assembly mitotic...
Abstract HELLS/LSH (Helicase, Lymphoid Specific) is a SNF2-like chromatin remodelling protein involved in DNA methylation. Its loss-of-function humans causes humoral immunodeficiency, called ICF4 syndrome (Immunodeficiency, Centromeric Instability, Facial anomalies). Here we show by our newly generated B-cell-specific Hells conditional knockout mouse model that HELLS plays pivotal role T-dependent B-cell responses. deficiency induces accelerated decay of germinal center (GC) B cells and...
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Almost all CpG-rich promoters in the mammalian genome are bound by multidomain FBXL10 protein (also known as KDM2B, JHDM1B, CXXC2, and NDY1). is expressed two isoforms: FBXL10-1, a longer form that contains an N-terminal histone demethylase domain with C-terminal F-box, CXXC, PHD, RING, leucine-rich repeat domains, FBXL10-2, shorter initiates at alternative internal exon which lacks but retains other annotated domains. Selective deletion of Fbxl10-1 had been reported to produce low...
Abstract The reversible glycosylation of nuclear and cytoplasmic proteins (O-GlcNAcylation) is catalyzed by a single enzyme, namely O-GlcNAc transferase (OGT). mammalian Ogt gene X-linked it essential for embryonic development the viability proliferating cells. We perturbed OGT’s function in vivo creating murine allelic series four amino acid substitutions reducing catalytic activity to range degrees. severity lethality was proportional degree impairment catalysis, demonstrating that...
In a previous paper Najean et al. have proposed “mamillary” model to account for iron metabolism in man and animals under normal conditions (1). The is based on the concept that biexponential fall-off curve of plasma radioactivity after vivo labeling transferrin with 59Fe due small non-heme, noncirculating pool (pool Q2 model, ref. 1) which can exchange transferrin. According this must be distributed throughout whole body. If validated, characteristics good agreement those calculated Q2,...
A 40‐year‐old woman splenectomized 17 years previously for hereditary haemolytic anaemia was investigated in our laboratory because of persistent conjunctival subic‐terus associated with compensated haemolysis. The results the autohaemolysis and osmotic fragility tests were similar to those usually observed spherocytosis. Red cell enzyme assays indicated a decreased amount kinetically normal enolase. genetic transmission this defect could not be established since only other affected member...
The tripartite motif-containing protein 66 (TRIM66, also known as TIF1-delta) is a PHD-Bromo–containing primarily expressed in post-meiotic male germ cells spermatids. Biophysical assays showed that the TRIM66 PHD-Bromodomain binds to H3 N-terminus only when lysine 4 unmethylated. We addressed TRIM66’s role reproduction by loss-of-function genetics mouse. Males homozygous for Trim66-null mutations produced functional spermatozoa. Round spermatids lacking up-regulated network of genes...