A5017670738- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Vascular Malformations and Hemangiomas
- RNA modifications and cancer
- Soft tissue tumor case studies
- Salivary Gland Tumors Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
- Vascular Tumors and Angiosarcomas
- Renal cell carcinoma treatment
- RNA Research and Splicing
- Oral and Maxillofacial Pathology
- Connective tissue disorders research
- Coronary Interventions and Diagnostics
- Cancer-related gene regulation
- Neuroblastoma Research and Treatments
- Pluripotent Stem Cells Research
- Chromatin Remodeling and Cancer
- Soft tissue tumors and treatment
- Renal and related cancers
- Renal and Vascular Pathologies
- RNA and protein synthesis mechanisms
- Fibroblast Growth Factor Research
- Zebrafish Biomedical Research Applications
- Ubiquitin and proteasome pathways
Centre National de la Recherche Scientifique
2013-2024
Laboratoire de Biologie du Développement
2016-2024
Institut Curie
2015-2024
Université Paris Sciences et Lettres
2016-2024
Inserm
2014-2024
Sorbonne Université
2014-2024
Université Paris Cité
2024
Hôpital Lariboisière
2001-2024
Assistance Publique – Hôpitaux de Paris
1999-2024
École Normale Supérieure
2021
Hotspot mutations in the spliceosome gene SF3B1 are reported ∼20% of uveal melanomas. is involved 3'-splice site (3'ss) recognition during RNA splicing; however, molecular mechanisms its mutation have remained unclear. Here we show, using RNA-Seq analyses melanoma, that SF3B1(R625/K666) results deregulated splicing at a subset junctions, mostly by use alternative 3'ss. Modelling differential junctions SF3B1(WT) and cell lines demonstrates splice pattern strictly depends on status...
Polycomb Group (PcG) proteins maintain transcriptional repression throughout development, mostly by regulating chromatin structure. Repressive Complex 2 (PRC2), a component of the machinery, is responsible for methylation histone H3 lysine 27 (H3K27me2/3). Jarid2 was previously identified as cofactor PRC2, PRC2 targeting to and its enzymatic activity. Deletion leads impaired orchestration gene expression during cell lineage commitment. Here, we reveal an unexpected crosstalk between with...
Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) adaptive increase artery diameter response a chronic blood flow, an arteriovenous fistula was constructed between left common carotid (CCA) external jugular vein 22 New Zealand White rabbits, NO synthesis inhibited 14 animals by long-term administration N G -nitro- l -arginine-methyl ester...
Tears in the internal elastic lamina (IEL) can be observed after chronic increases arterial blood flow, suggesting a potential role for matrix metalloproteinases (MMPs) flow-induced vascular remodeling. We undertook to study this phenomenon by constructing an arteriovenous fistula (AVF) between left common carotid artery (CCA) and external jugular vein rabbits. The diameter of flow-loaded CCA increased 13.6+/-1.8% day 3 construction AVF compared with right (n=4, P:<0.01) 40.7+/-7.5% day-15...
Abstract Long non‐coding RNA s (lnc s) play diverse roles in physiological and pathological processes. Several lnc have been suggested to modulate gene expression by guiding chromatin‐modifying complexes specific sites the genome. However, besides example of Xist, clear‐cut evidence demonstrating this novel mode regulation remains sparse. Here, we focus on HOTAIR , a that is overexpressed several tumor types previously proposed key role silencing through direct recruitment Polycomb...
Abstract In Drosophila , a complex consisting of Calypso and ASX catalyzes H2A deubiquitination has been reported to act as part the Polycomb machinery in transcriptional silencing. The mammalian homologs these proteins (BAP1 ASXL1/2/3, respectively), are frequently mutated various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover unanticipated role for BAP1 gene activation. This...
Alterations of chromatin modifiers are frequent in cancer, but their functional consequences often remain unclear. Focusing on the Polycomb protein EZH2 that deposits H3K27me3 (trimethylation Lys27 histone H3) mark, we showed its high expression solid tumors is a consequence, not cause, tumorigenesis. In mouse and human models, dispensable for prostate cancer development restrains breast High results from tight coupling to proliferation ensure homeostasis. However, this process malfunctions...
The hierarchical organization of eukaryotic chromatin plays a central role in gene regulation, by controlling the extent to which transcription machinery can access DNA. histone variants H3.3 and H2A.Z have recently been identified as key regulatory players this process, but underlying molecular mechanisms they permit or restrict expression remain unclear. Here, we investigated function on dynamics Polycomb-mediated silencing.Our ChIP-seq analysis reveals that mouse embryonic stem (mES)...
A variant erythroferrone contributes to hepcidin modulation and systemic iron accumulation in patients with SF3B1 -mutated myelodysplastic syndrome.
Genetic mutations affecting chromatin modifiers are widespread in cancers. In malignant peripheral nerve sheath tumors (MPNSTs), Polycomb repressive complex 2 (PRC2), which plays a crucial role gene silencing, is inactivated through recurrent core subunits embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12), but PRC2’s main catalytic subunit enhancer (EZH2) have never been found. This contrast to myeloid lymphoid malignancies, harbor frequent loss-of-function...
Abstract Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS mutations in other splicing factor genes SRSF2 or U2AF1 . Molecular bases of these divergences are poorly understood. Here we find that -mutated show reduced R-loop formation predominating bodies associated intron retention reduction, not found - MDS. Compared to erythroblasts SRSF2- patients, exhibit augmented DNA synthesis, accelerated replication forks, and...
Mutations in chromatin regulators are widespread cancer. Among them, the histone H3 lysine 27 methyltransferase Polycomb Repressive Complex 2 (PRC2) shows distinct alterations according to tumor type. This specificity is poorly understood. Here, we model several PRC2 one isogenic system reveal their comparative effects. Focusing then on lymphoma-associated EZH2 mutations, show that Ezh2
Parental allele-specific expression of imprinted genes is mediated by imprinting control regions (ICRs) that are constitutively marked DNA methylation imprints on the maternal or paternal allele. Mono-allelic strictly required for process and has to be faithfully maintained during entire life-span. While regulation itself well understood, mechanisms whereby opposite allele remains unmethylated unclear. Here, we show in mouse, at maternally methylated ICRs, allele, which associated with...
The objective of this study was to compare the repartition in renal arterial vasculature tris-acryl gelatin microspheres (TGMS) and polyvinyl alcohol (PVAMS) 3 calibers (500-700, 700-900, 900-1200 microm).Twelve kidneys from 6 adult sheep were embolized histologically analyzed. number size vessels measured, as well deformation TGMS PVAMS, histologic location according a classification 5 zones kidney.Two hundred eighty-four measured. diameter occluded increased when caliber used for...