A5081826213- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- DNA Repair Mechanisms
- Genetics and Neurodevelopmental Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Plant Molecular Biology Research
- Neurogenetic and Muscular Disorders Research
- Protein Degradation and Inhibitors
Centre National de la Recherche Scientifique
2011-2025
Université Paris Cité
2015-2025
Epigénétique et Destin Cellulaire
2015-2025
Epigenomics (Germany)
2024
Sorbonne Université
2014-2020
Dynamique du noyau
2011-2020
Institut Curie
2011-2020
Université Paris Sciences et Lettres
2019-2020
Université des Lettres et des Sciences Humaines de Bamako
2018
Sorbonne Paris Cité
2015-2016
DNA replication is a challenge for the faithful transmission of parental information to daughter cells, as both and chromatin organization must be duplicated. Replication stress further complicates safeguard epigenome integrity. Here, we investigate histone variants H3.3 H3.1 during replication. We follow their distribution relative timing, first in genome and, second, 3D using super-resolution microscopy. find that mark early- late-replicating chromatin, respectively. In nucleus, forms...
Centromeric protein A (CENP-A) is the epigenetic mark of centromeres. CENP-A replenishment necessary in each cell cycle to compensate for dilution associated DNA replication, but how this achieved mechanistically largely unknown. We have developed an assay using Xenopus egg extracts that can recapitulate spatial and temporal specificity deposition observed human cells, providing us with a robust vitro system amenable molecular dissection. Here we show depends on Holliday junction–recognizing...
Centromeric protein A (CENP-A) is the epigenetic mark of centromeres. CENP-A replenishment necessary in each cell cycle to compensate for dilution associated DNA replication, but how this achieved mechanistically largely unknown. We have developed an assay using Xenopus egg extracts that can recapitulate spatial and temporal specificity deposition observed human cells, providing us with a robust vitro system amenable molecular dissection. Here we show depends on Holliday junction-recognizing...
Abstract The HIRA histone chaperone complex deposits the variant H3.3 onto chromatin in a DNA synthesis-independent manner. It comprises three identified subunits, HIRA, UBN1 and CABIN1, however functional oligomerization state of has not been investigated. Here we use biochemical crystallographic analysis to show that subunit forms stable homotrimer binds two subunits CABIN1 vitro. A mutant is defective formation interacts less efficiently with enriched at damage sites upon UV irradiation...
Abstract Vertebrates exhibit specific requirements for replicative H3 and non-replicative H3.3 variants during development. To disentangle whether this involves distinct modes of deposition or unique functions once incorporated into chromatin, we combined studies in Xenopus early development with chromatin assays. Here investigate the extent to which mutated at residues that differ from H3.2 rescue developmental defects caused by depletion. Regardless pathway, only residue 31—a serine can...
Abstract Recently, the repertoire of human small nucleolar noncoding RNAs (snoRNAs) and their potential functions has expanded with discovery new snoRNAs messenger RNA (mRNA) targets, for which snoRNA-guided modifications may influence stability, translatability, splicing. We previously identified that are abundant in healthy muscle progenitor cells. In this study, we demonstrated SNORA40 SNORA70 loss-of-function impairs myogenic differentiation. Interestingly, gain-of-function can rescue...
Correct chromosome segregation requires a unique chromatin environment at centromeres and in their vicinity. Here, we address how the deposition of canonical H2A H2A.Z histone variants is controlled pericentric heterochromatin (PHC). While euchromatin newly-synthesized are deposited throughout cell cycle, reveal two discrete waves PHC: during mid-late S phase replication-dependent manner for H2A, G1 H2A.Z. This cycle restriction lost when features altered, leading to accumulation domain....
ABSTRACT The packaging of DNA into nucleosomes represents a challenge for transcription. Nucleosome disruption and histone eviction enables RNA Polymerase II progression through DNA, process that compromises chromatin integrity the maintenance epigenetic information. Here, we used imaging SNAP-tag system to distinguish new old histones monitor re-assembly coupled transcription in cells. First, uncovered loss both variants H3.1 H3.3 depends on transcriptional activity, with major effect H3.3....
ABSTRACT Since its discovery as an Immunodeficiency with Centromeric instability and Facial anomalies syndrome-causative gene, ZBTB24 has emerged a key player in DNA methylation, immunity development. By extensively analyzing genomic functions ICF-relevant mouse human cellular models, we revealed here multiple facets transcription factor, roles immune response-related genes expression also early embryonic Using constitutive Zbtb24 ICF-like mutant auxin-inducible degron system stem cells,...
Skeletal muscle terminal differentiation starts with the commitment of pluripotent mesodermal precursor cells to myoblasts. These have still ability proliferate or they can differentiate and fuse into multinucleated myotubes, which maturate further form myofibers. is orchestrated by coordinated action various transcription factors, in particular members Muscle Regulatory Factors MRFs (MyoD, Myogenin, Myf5, MRF4), also called myogenic bHLH factors family. cooperate chromatin-remodeling...
Overactivation of the transforming growth factor-β (TGFβ) signaling in Duchenne muscular dystrophy (DMD) is a major hallmark disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated role SETDB1 (SET domain, bifurcated 1), histone lysine methyltransferase involved differentiation. Our data show that, following TGFβ induction, accumulates nuclei healthy myotubes while being already present DMD where constitutively activated. Transcriptomics revealed that depletion...
Abstract Since its discovery as a causative gene of the Immunodeficiency with Centromeric instability and Facial anomalies syndrome, ZBTB24 has emerged key player in DNA methylation, immunity development. By extensively analyzing genomic functions ICF-relevant mouse human cellular models, we document here multiple facets transcription factor, roles immune response-related genes expression also early embryonic Using constitutive Zbtb24 ICF-like mutant an auxin-inducible degron system stem...
Skeletal muscle terminal differentiation starts with the commitment of pluripotent mesodermal precursor cells to myoblasts. These have still ability proliferate or they can differentiate and fuse into multinucleated myotubes, which maturate further form myofibers. is orchestrated by coordinated action various transcription factors, in particular members Muscle Regulatory Factors MRFs (MyoD, Myogenin, Myf5, MRF4), also called myogenic bHLH factors family. cooperate chromatin-remodeling...
SUMMARY Overactivation of the TGFβ signaling in Duchenne muscular dystrophy (DMD) is a major hallmark disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated role SETDB1, histone lysine methyltransferase involved differentiation. Our data show that, following induction, SETDB1 accumulates nuclei healthy myotubes, while being already present DMD myotubes where constitutively activated. Interestingly, transcriptomics revealed that depletion leads downregulation...
Abstract The closely related replicative H3 and non-replicative H3.3 variants show specific requirement during development in vertebrates. Whether it involves distinct mode of deposition or unique roles once incorporated into chromatin remains unclear. To disentangle the two aspects, we took advantage Xenopus early combined with assays. Our previous work showed that Xenopus, depletion variant impairs at gastrulation, without compensation through provision H3.2. We systematically mutated each...