A5073147629- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- RNA Research and Splicing
- Circular RNAs in diseases
- Epigenetics and DNA Methylation
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Tissue Engineering and Regenerative Medicine
- Genetic factors in colorectal cancer
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Chromosomal and Genetic Variations
- RNA Interference and Gene Delivery
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- FOXO transcription factor regulation
- Neonatal Respiratory Health Research
- Genomic variations and chromosomal abnormalities
- Prostate Cancer Diagnosis and Treatment
- Amino Acid Enzymes and Metabolism
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Renal cell carcinoma treatment
- Cancer-related gene regulation
- Advanced Proteomics Techniques and Applications
Epigénétique et Destin Cellulaire
2015-2024
Université Paris Cité
2015-2024
Centre National de la Recherche Scientifique
2015-2024
University Health Network
2018-2023
Princess Margaret Cancer Centre
2018-2023
Ontario Institute for Cancer Research
2023
Sorbonne Paris Cité
2015-2017
University of Bari Aldo Moro
1998
University of Reggio Calabria
1998
Pediatrics and Genetics
1998
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...
Tumor progression upon treatment arises from preexisting resistant cancer cells and/or adaptation of persister committing to an expansion phase. Here, we show that evasion viral mimicry response allows the growth taxane-resistant triple-negative breast (TNBC). This is enabled by epigenetic state adapted taxane-induced metabolic stress, where DNA hypomethylation over loci enriched in transposable elements (TE) compensated large chromatin domains H3K27me3 warrant TE repression. creates a...
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...
Abstract Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved disease onset progression through both androgen receptor-dependent receptor-independent mechanisms. Despite its oncogenic properties however, regulation of expression remains unknown. Here, we identify set six cis -regulatory elements regulatory plexus harboring somatic...
Abstract Transposable elements hold regulatory functions that impact cell fate determination by controlling gene expression. However, little is known about the transcriptional machinery engaged at transposable in pluripotent and mature versus oncogenic states. Through positional analysis over repetitive DNA sequences of H3K27ac chromatin immunoprecipitation sequencing data from 32 normal states, we report pluripotent/stem state–specific “regulatory elements.” Pluripotent/stem are binding...
Objective. To provide indications for high-resolution computed tomography (HRCT) of the chest in patients with cystic fibrosis (CF). Design. We compared HRCT and conventional radiography (CCR) scores assessed their correlation clinical pulmonary function tests. Setting. Department Pediatrics, Federico II University, Naples, Italy. Subjects. A total 30 CF 6.75 to 24 years age. Results. CCR correlated highly (r = −0.8) 0.5) scores, whereas were not related scores. Of all specific findings,...
Alu are high copy number interspersed repeats that have accumulated near genes during primate and human evolution. They a pervasive source of structural variation in modern humans. Impacts insertions may on gene expression not well understood, although some been associated with quantitative trait loci (eQTLs). Here, we directly test regulatory effects polymorphic isolation other variants the same haplotype. To screen insertion for those such effects, used ectopic luciferase reporter assays...
Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting immune response defects. Interestingly, recent findings report that shapes intragenic CpG-methylation highly-transcribed genes. However, how DNMT3B-dependent epigenetic network modulates transcription whether ICF1-specific...
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...
Mouse embryonic stem cells (ESCs) and epiblast (EpiSCs) represent naive primed pluripotency states, respectively, are maintained in vitro by specific signalling pathways. Furthermore, ESCs cultured serum-free medium with two kinase inhibitors (2i-ESCs) thought to be the ground naïve pluripotent state. Here, we present a comparative study of epigenetic transcriptional states pericentromeric heterochromatin satellite sequences found these states. We show that 2i-ESCs distinguished from other...
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...
Pulmonary disease is a complication of Gaucher (GD), lysosomal disorder due to the deficiency glucocerebrosidase. Lung involvement was investigated through chest radiography, high-resolution computed tomography chest, pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13 Italian GD patients, six homoallelic for L444P mutation (Group A), seven with various genotypes B). Echocardiography transcutaneous tension measurement room air after breathing 100% were performed...
Prostate cancer is a heterogeneous disease whose progression linked to genome instability. However, the impact of this instability on noncoding and its three-dimensional organization aid unclear. Using primary benign tumor tissue, we find high concordance in higher-order organization. This argues for constraints topology prostate genomes. Nonetheless, identified changes focal chromatin interactions, typical loops bridging cis-regulatory elements, showed how structural variants can induce...
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,...
SUMMARY Cancer cell survival upon cytotoxic drug exposure leads to changes in identity, dictated by the epigenome. Several metabolites serve as substrates or co-factors chromatin-modifying enzymes, suggesting that metabolic can underlie change fate. Here, we show progression of triple-negative breast cancer (TNBC) taxane-resistance is characterized altered methionine metabolism and S-adenosylmethionine (SAM) availability, giving rise DNA hypomethylation regions enriched for transposable...
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...
Abstract Prostate cancer is a heterogeneous disease whose progression linked to genome instability. However the impact of this instability on three-dimensional chromatin organization and how drives unclear. Using primary benign tumour tissue, we find high concordance in higher-order across normal prostate cells. This argues for constraints topology genomes. Nonetheless, identify changes focal interactions show structural variants can induce these guide cis -regulatory element hijacking. Such...
Abstract Despite most acute myeloid leukemia (AML) patients achieving complete remission after induction chemotherapy, two-thirds will relapse with fatal disease within five years. AML is organized as a cellular hierarchy sustained by stem cells (LSC) at the apex, LSC properties directly linked to tumor progression, therapy failure, and 1–5 . central role of in poor patient outcomes, little known about genetic determinants driving their stemness properties. As LSCs share many functional...