A5063412451- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Genetic Syndromes and Imprinting
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Angiogenesis and VEGF in Cancer
- Neonatal Respiratory Health Research
- Genomic variations and chromosomal abnormalities
- Telomeres, Telomerase, and Senescence
- Pediatric health and respiratory diseases
- Amino Acid Enzymes and Metabolism
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Genomics and Rare Diseases
- Cancer Cells and Metastasis
- Autism Spectrum Disorder Research
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Effects and risks of endocrine disrupting chemicals
- MicroRNA in disease regulation
- Lymphatic System and Diseases
Epigénétique et Destin Cellulaire
2010-2024
Sorbonne Paris Cité
2011-2024
Université Paris Cité
2014-2024
Centre National de la Recherche Scientifique
2014-2024
Inserm
2006-2023
Institut Cochin
2023
Délégation Paris 7
2011-2015
Université Paris 8
2015
Research Institute Hospital 12 de Octubre
2012
Hôpital Saint-Louis
2007
Abstract The life-threatening Immunodeficiency, Centromeric Instability and Facial Anomalies (ICF) syndrome is a genetically heterogeneous autosomal recessive disorder. Twenty percent of patients cannot be explained by mutations in the known ICF genes DNA methyltransferase 3B or zinc-finger BTB domain containing 24. Here we report cell division cycle associated 7 helicase, lymphoid-specific 10 unexplained cases. Our data highlight genetic heterogeneity syndrome; however, they provide...
The steroid receptor RNA activator (SRA) has the unusual property to function as both a non-coding (ncRNA) and protein SRAP. SRA ncRNA is known increase activity of range nuclear receptors well master regulator muscle differentiation MyoD. contribution either or influenced by alternative splicing first intron, retention which disrupts SRAP open reading frame. We reported here that ratio between coding isoforms increased during myogenic human satellite cells but not myotonic dystrophy patient...
Non-coding RNAs are emerging as key players in many fundamental biological processes, including specification of higher-order chromatin structure. We examined the implication RNA transcribed from mouse centromeric minor satellite repeats formation and function centromere-associated complexes. Here we show that levels vary during cell-cycle progression, peaking G2/M phase, concomitant with accumulation proteins chromosomal passenger complex near centromere. Consistent this, describe murine...
Methylation of cytosine residues within the CpG dinucleotide in mammalian cells is an important mediator gene expression, genome stability, X-chromosome inactivation, genomic imprinting, chromatin structure, and embryonic development. The majority sites methylated a nonrandom fashion, raising question how DNA methylation distributed along genome. Here, we focused on functions methyltransferase-3b (Dnmt3b), which deregulated activity linked to several human pathologies. We generated Dnmt3b...
Abstract DNA:RNA hybrids, nucleic acid structures with diverse physiological functions, can disrupt genome integrity when dysregulated. Human telomeres were shown to form hybrids the lncRNA TERRA, yet formation and distribution of these among telomeres, their regulation cellular effects remain elusive. Here we predict confirm in several human cell types that at many subtelomeric telomeric regions. We demonstrate ICF syndrome cells, which exhibit short elevated TERRA levels, are enriched for...
DNA methylation (DNAme) is a key epigenetic mark that regulates critical biological processes maintaining overall genome stability. Given its pleiotropic function, studies of DNAme dynamics are crucial, but currently available tools to interfere with have limitations and major cytotoxic side effects. Here, we present cell models allow inducible reversible modulation through DNMT1 depletion. By dynamically assessing whole locus-specific effects induced passive demethylation divisions, reveal...
Environmental chemicals may affect human health by disrupting endocrine function. Their possible role in the mammary gland and breast tumors is still unknown. Previous studies have demonstrated that vascular endothelial growth factor (VEGF), a key angiogenesis tumor progression, an estrogen-regulated gene. We analyzed whether VEGF expression regulated different xenoestrogens several cancer cells, MELN (derived from MCF-7) MELP MDA-MB-231) stably expressing estrogen receptor α (ERα); these...
Mutations in CDCA7 and HELLS that respectively encode a CXXC-type zinc finger protein an SNF2 family chromatin remodeler cause immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome types 3 4. Here, we demonstrate the classical nonhomologous end joining (C-NHEJ) proteins Ku80 Ku70, as well HELLS, coimmunoprecipitated with CDCA7. The coimmunoprecipitation of repair was sensitive to nuclease treatment ICF3 mutation impairs its binding. functional importance these...
Alterations of DNA methylation landscapes and machinery are a hallmark many human diseases. A prominent case is the ICF syndrome, rare autosomal recessive immunological/neurological disorder diagnosed by loss at (peri)centromeric repeats its associated chromosomal instability. It caused mutations in de novo methyltransferase DNMT3B about half patients (ICF1). In remainder, striking identification factors devoid activity, ZBTB24 (ICF2), CDCA7 (ICF3) or HELLS (ICF4), raised key questions...
DNA methylation mostly occurs within the context of CpG dinucleotides and is essential for embryonic development gene repression. It generally accepted that methyltransferases carry out specific non-overlapping functions, Dnmt3a Dnmt3b being responsible establishment around time implantation Dnmt1 ensuring faithfully copied to daughter cells via what has come be known as "maintenance methylation." This longstanding view been challenged over years with observation alone incapable perfect...
Abstract Chromosome segregation during mitosis is monitored by the mitotic checkpoint and dependent upon DNA methylation. ZBTB4 a mammalian epigenetic regulator with high affinity for methylated CpGs that localizes at pericentromeric heterochromatin frequently downregulated in cancer. Here, we report decreased expression correlates genome instability across many frequent human cancers. In cell lines, depletion was sufficient to increase prevalence of micronuclei binucleated cells parallel...
Centromeres are chromosomal domains essential for genomic stability. We report here the remarkable transcriptional and epigenetic perturbations at murine centromeres in genotoxic stress conditions. A strong selective activation of centromeric repeats is detected within hours. This followed by disorganization with striking delocalization nucleosomal CENP-A, key determinant centromere identity function, a mechanism requiring active transcription repeats, DNA Damage Response (DDR) effector ATM...
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that caused by mutations in either DNMT3B, ZBTB24, CDCA7, HELLS, or yet unidentified gene(s). Previously, we reported the CDCA7/HELLS chromatin remodeling complex facilitates non-homologous end-joining. Here, show same required for accumulation of proteins on nascent DNA, including DNMT1/UHRF1 maintenance DNA methylation as well involved resolution prevention R-loops composed...
Background Endothelial dysfunction has been implicated in the pathogenesis of diverse pathologies ranging from vascular and immune diseases to cancer. TNF-α is one mediators endothelial through activation transcription factors, including NF-κB. While HUVEC (macrovascular cells) have largely used past, here, we documented an NF-κB gene signature TNFα-stimulated microvascular cells HMEC often tumor angiogenesis studies. Methodology/Principal Findings We measured mRNA expression 55 related...
Immunodeficiency Centromeric Instability and Facial anomalies (ICF) is a rare autosomal recessive disease characterized by reduction in serum immunoglobulins with severe recurrent infections, facial dysmorphism, more variable symptoms including mental retardation. ICF directly related to genomic methylation defect that mainly affects juxtacentromeric heterochromatin regions of certain chromosomes, leading chromosomal rearrangements constitute hallmark this syndrome upon cytogenetic testing....
Human telomeres and adjacent subtelomeres are packaged as heterochromatin. Subtelomeric DNA undergoes methylation during development by methyltransferase 3B (DNMT3B), including the CpG-rich promoters of long non-coding RNA (TERRA) embedded in these regions. The factors that direct DNMT3B to human maintain this throughout lifetime yet unknown. importance subtelomeric is manifested through abnormal telomeric phenotype Immunodeficiency, Centromeric instability Facial anomalies (ICF) syndrome...
Abstract Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations either DNA methyltransferase (DNMT)3B, zinc finger BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. However, the causative genes of a few ICF patients remain unknown. We, herein, identified ubiquitin-like with plant homeodomain really interesting new gene domains 1 (UHRF1) as novel one such patient atypical symptoms. This...
The BS69 protein has been commonly described as a co-repressor associated with various transcription factors. However, this hypothesis relied predominantly on overexpression of tagged proteins due to the lack reliable antibody. We present for first time complete sequence and valuable tools characterize endogenous protein. show that full-length protein, well minor alternatively spliced isoforms, is ubiquitously expressed, nuclear, associates chromatin mitotic chromosomes. Accordingly,...