A5068197353- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Lung Cancer Diagnosis and Treatment
- Genomic variations and chromosomal abnormalities
- Immunotherapy and Immune Responses
- Plant Genetic and Mutation Studies
- Actinomycetales infections and treatment
- Nuclear Structure and Function
- Plant Molecular Biology Research
- Sphingolipid Metabolism and Signaling
- Amoebic Infections and Treatments
Sorbonne Université
2023-2025
Institut Curie
2019-2025
Université Paris Sciences et Lettres
2019-2025
Centre National de la Recherche Scientifique
2019-2025
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
2019-2023
European Institute of Oncology
2013-2019
Vita-Salute San Raffaele University
2010-2014
International Society for Experimental Hematology
2014
Polycomb repressive complexes 1 and 2 (PRC1 PRC2) control cell identity by establishing facultative heterochromatin domains at common sets of target genes. PRC1, which deposits H2Aub1 through the E3 ligases RING1A/B, forms six biochemically distinct subcomplexes depending on assembled PCGF protein (PCGF1-PCGF6); however, it is yet unclear whether these have also specific activities. Here we show that PCGF1 PCGF2 largely compensate for each other, while other proteins high levels specificity...
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S phase, but not other cell-cycle stages, caused accumulation R...
Abstract DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It yet unclear if UHRF1 functions solely by stimulating DNMT1, or it has important additional functions. Using degron alleles, we show that depletion causes a much greater loss of than DNMT1 depletion. This not caused passive demethylation as UHRF1-depleted cells proliferate more slowly DNMT1-depleted cells. Instead, bioinformatics, proteomics genetics...
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...
Abstract CD1 molecules present lipid antigens to T cells. An intriguing subset of human cells recognize CD1‐expressing without deliberately added lipids. Frequency, distribution, clonal composition, naïve‐to‐memory dynamic transition these self‐reactive remain largely unknown. By screening libraries T‐cell clones, generated from CD4 + or − CD8 double negative (DN) sorted the same donors, and by limiting dilution analysis, we find that frequency is unexpectedly high in both subsets, range...
The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity cancer. PcGs silence the expression tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb p53 functions. Enhanced PcG frequent human tumours, inhibition has been proposed as strategy for cancer treatment. However, recurrent inactivation pRb/p53 responses in cancers raises question regarding proteins affect cellular independently from this checkpoint. Here we...
T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity potential antileukemia effects. We report self-reactive a novel class self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which accumulated leukemia cells. Primary acute myeloid B cell blasts express CD1 molecules. mLPA-specific efficiently CD1c+ poorly nontransformed...
Errors during cell division lead to aneuploidy, which is associated with genomic instability and transformation. In response cells activate the tumour suppressor p53 elicit a surveillance mechanism that halts proliferation promotes senescence. The molecular sensors trigger this checkpoint are unclear. Here, using tunable system of chromosome mis-segregation, we show mitotic errors nuclear deformation, softening, lamin heterochromatin alterations, leading rapid p53/p21 activation upon exit in...
Stem cell identity maintenance by PRC1 repressive activity is influenced TFs and epigenetic landscape of specific types.
Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several induce leukemogenesis activating Hox gene (Hox-activating fusions), others impinge on pathways that do not involve activation genes (non-Hox-activating fusions). It has been postulated one main properties HOXA9 transcription factor its ability to control p16/p19 tumor suppressor locus (Cdkn2a), thereby compensating...
CENP-A is the histone H3 variant necessary to specify location of all eukaryotic centromeres via its targeting domain and either one terminal regions. In humans, several post-translational modifications occur on CENP-A, but their role in centromere function remains controversial. One these phosphorylation serine 7, has been proposed control assembly function. Here, using gene at both endogenous alleles replacement human cells, we demonstrate that a cannot be phosphorylated 7 maintains...
ABSTRACT 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 untransformed cancer cell models allow inducible reversible global modulation through DNMT1 depletion. By dynamically assessing the effects induced passive...
Abstract Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S-phase, but not other cell cycle stages, caused...
The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests an intrinsic instability centromeres, unique chromosomal loci built on large stretches repetitive sequences. causes behind this fragility the mechanisms acting to preserve centromere integrity remain elusive. Here, we show that replication stress, a hallmark (pre-)cancerous lesions, promotes non-random breakage mitosis, also observed panel ex-vivo patient-derived ovarian cancer models along with...