A5001385390- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Chromosomal and Genetic Variations
- Glioma Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Radiomics and Machine Learning in Medical Imaging
- Circular RNAs in diseases
- Acute Myeloid Leukemia Research
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Caveolin-1 and cellular processes
- DNA Repair Mechanisms
- Congenital Diaphragmatic Hernia Studies
- Chronic Lymphocytic Leukemia Research
- Chromatin Remodeling and Cancer
- Assisted Reproductive Technology and Twin Pregnancy
- Antimicrobial Peptides and Activities
Genetique Reproduction and Developpement
2016-2024
Centre National de la Recherche Scientifique
2015-2024
Inserm
2015-2024
Université Clermont Auvergne
2015-2024
Université de Montpellier
2008-2018
Institutt for Grafiske Medier
2018
Institut d'Investigació Biomédica de Bellvitge
2013-2016
Clermont-Ferrand’s Superior National School of Chemistry
2016
Duran i Reynals Hospital
2014-2015
Université Toulouse III - Paul Sabatier
2014
Differential methylation between the two alleles of a gene has been observed in imprinted regions, where one allele occurs on parent-of-origin basis, inactive X-chromosome females, and at those loci whose is driven by genetic variants. We have extensively characterized substantial range normal human tissues, reciprocal genome-wide uniparental disomies, hydatidiform moles, using combination whole-genome bisulfite sequencing high-density microarrays. This approach allowed us to define profiles...
Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present data describing fate germline-derived humans. With exception a few known paternally methylated germline differentially (DMRs) domains, demonstrate sperm-derived is reprogrammed by blastocyst stage development. In contrast large...
Genomic imprinting is the parent-of-origin-specific allelic transcriptional silencing observed in mammals, which governed by DNA methylation established gametes and maintained throughout development. The frequency extent of epimutations associated with nine reported syndromes varies because it evident that aberrant preimplantation maintenance imprinted differentially methylated regions (DMRs) may affect multiple loci. Using a custom Illumina GoldenGate array targeting 27 DMRs, we profiled 65...
Genomic imprinting is the epigenetic marking of genes that results in parent-of-origin monoallelic expression. Most imprinted domains are associated with differentially DNA methylated regions (DMRs) originate gametes, and maintained somatic tissues after fertilization. This allelic methylation profile a plethora histone tail modifications orchestrates higher order chromatin interactions. The mouse chromosome 15 cluster contains multiple brain-specific maternally expressed transcripts...
For the past three decades, assisted reproductive technologies (ART) have revolutionized infertility treatments. The use of ART is thought to be safe. However, early investigations suggested that children born as a result had higher risk diseases with epigenetic etiologies, including imprinting disorders caused by lack maternal methylation at control elements. In addition, large epidemiology studies highlighted an increased obstetric complications, severe intrauterine growth restriction...
Parental genomic imprinting at the Igf2/H19 locus is controlled by a methylation-sensitive CTCF insulator that prevents access of downstream enhancers to Igf2 gene on maternal chromosome. However, paternal chromosome, it remains unclear whether long-range interactions with are restricted promoters or they encompass entire body. Here, using quantitative chromosome conformation capture assay, we show that, in mouse liver, endodermal have low contact frequencies but display, strong intragenic...
The myogenic regulatory factor Myod and insulin-like growth 2 (Igf2) have been shown to interact in vitro during differentiation. In order understand how they vivo, we produced double-mutant mice lacking both the Igf2 genes. Surprisingly, these display neonatal lethality due severe diaphragm atrophy. Alteration of muscle development occurs as early 15.5 days post-coitum embryos leads a defect terminal differentiation progenitor cells. A negative-feedback loop was detected between embryonic...
Cancer is as much an epigenetic disease a genetic one; however, the interplay between these two processes unclear. Recently, it has been shown that large proportion of DNA methylation variability can be explained by allele-specific (ASM), either at classical imprinted loci or those regulated underlying variants. During recent screen for differentially methylated regions, we identified genomic interval overlapping non-coding nc886 RNA (previously known vtRNA2-1) atypical ASM shows variable...
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...
It was recently shown that a long non-coding RNA (lncRNA), we named the 91H (i.e. antisense H19 transcript), is overexpressed in human breast tumours and contributes trans to expression of Insulin-like Growth Factor 2 (IGF2) gene on paternal chromosome. Our preliminary experiments suggested an transcript having similar function may also be conserved mouse. In present work, further characterise mouse and, using genetic complementation approach KO myoblast cells, show ectopic can up-regulate...
CpG islands (CGI) marked by bivalent chromatin in stem cells are believed to be more prone aberrant DNA methylation tumor cells. The robustness and genome-wide extent of this instructive program different cancer types remain determined. To address issue we developed a user-friendly approach integrate the cell signature customized analyses. We used publicly available ChIP-sequencing datasets several human embryonic (hESC) lines determine genome-wide. then created annotated lists...
The cornea is a transparent, avascular tissue that acts as the major refractive surface of eye. Corneal transparency, assured by inner stroma, vital for this role. Disruption in stromal transparency can occur some inherited or acquired diseases. As consequence, light entering eye blocked distorted, leading to decreased visual acuity. Possible treatment restoring could be via viral-based gene therapy. stroma particularly amenable strategy due its immunoprivileged nature and low turnover rate....
In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution methylation–dependent and –independent mechanisms alterations at CpG island/promoter-associated genes cancer, we studied 70 samples adult glioma, a widespread type brain tumor, classified according...
In human, the 39 coding HOX genes and 18 referenced noncoding antisense transcripts are arranged in four genomic clusters named HOXA, B, C, D. This highly conserved family belongs to homeobox class of that encode transcription factors required for normal development. Therefore, gene deregulation might contribute development many cancer types. Here, we study adult glioma, a common type primary brain tumor. We performed extensive molecular analysis tumor samples, classified according their...
Besides the consequences of retrotransposition, long interspersed element 1 (L1) retrotransposons can affect host genome through their antisense promoter. In addition to sense promoter, evolutionarily recent L1 retrotransposons, which are present in several thousand copies, also possess an anti-sense promoter that produce chimeric transcripts (LCT) composed 5' UTR followed by adjacent genomic sequence. The full extent LCT expression occurs a given tissue and whether disruption defense...
Paternal duplications of chromosome 6q24, a region that contains the imprinted PLAGL1 and HYMAI transcripts, are associated with transient neonatal diabetes mellitus. A common feature genes is they tend to cluster together, presumably as result sharing cis -acting regulatory elements. To determine extent this in human mouse, we have undertaken systematic analysis allelic expression DNA methylation mapping within an ∼1.4-Mb flanking PLAGL1/Plagl1 . We confirm all nine neighbouring...
Wilms tumor 1 (WT1) is over-expressed in numerous cancers with respect to normal cells, and has either a suppressor or oncogenic role depending on cellular context. This gene associated alternatively spliced transcripts, which initiate from two different unique first exons within the WT1 alternative (A)WT1 promoter intervals. Within hematological system, expression restricted CD34+/CD38- cells undetectable after differentiation. Detectable of this an excellent marker for minimal residual...
Despite the high efficiency of tyrosine kinase inhibitors (TKI), some patients with chronic myeloid leukemia (CML) will display residual disease that can become resistant to treatment, indicating intraclonal heterogeneity in chronic‐phase CML (CP‐CML). To determine basis this heterogeneity, we conducted first exhaustive characterization DNA methylation pattern sorted CP‐CML CD34 + CD15 − (immature) and (mature) cells at diagnosis (prior any treatment) compared it isolated from healthy donors...
We previously showed that genomic imprinting regulates matrix attachment region activities at the mouse Igf2 (insulin-like growth factor 2) locus and these are functionally linked to neighboring differentially methylated regions (DMRs). Here, we investigate similarly structured Dlk1/Gtl2 imprinted domain show in liver, G/C-rich intergenic germ line-derived DMR, a sequence involved domain-wide imprinting, is highly retained within nuclear fraction exclusively on paternal copy, reflecting its...
Abstract Background Despite its critical role for mammalian gene regulation, the basic structural landscape of chromatin in living cells remains largely unknown within chromosomal territories below megabase scale. Results Here, using 3C-qPCR method, we investigate contact frequencies at high resolution interphase several mouse loci. We find that, gene-rich loci, undergo a periodical modulation (every 90 to 100 kb) that affects dynamics over large genomic distances (a few hundred kilobases)....
Genomic imprinting is a complex epigenetic mechanism of transcriptional control that utilizes DNA methylation and histone modifications to bring about parent-of-origin specific monoallelic expression in mammals. Genes subject are often organised clusters associated with large non-coding RNAs (ncRNAs), some which have cis-regulatory functions. Here we undertaken detailed allelic analysis an imprinted domain on mouse proximal chromosome 10 comprising the paternally expressed Plagl1 gene. We...