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Dive into the research topics where Sylvain Guibert is active.

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Featured researches published by Sylvain Guibert.


Nature Genetics | 2010

Targets and dynamics of promoter DNA methylation during early mouse development

Julie Borgel; Sylvain Guibert; Yufeng Li; Hatsune Chiba; Dirk Schübeler; Hiroyuki Sasaki; Thierry Forné; Michael Weber

DNA methylation is extensively reprogrammed during the early phases of mammalian development, yet genomic targets of this process are largely unknown. We optimized methylated DNA immunoprecipitation for low numbers of cells and profiled DNA methylation during early development of the mouse embryonic lineage in vivo. We observed a major epigenetic switch during implantation at the transition from the blastocyst to the postimplantation epiblast. During this period, DNA methylation is primarily targeted to repress the germline expression program. DNA methylation in the epiblast is also targeted to promoters of lineage-specific genes such as hematopoietic genes, which are subsequently demethylated during terminal differentiation. De novo methylation during early embryogenesis is catalyzed by Dnmt3b, and absence of DNA methylation leads to ectopic gene activation in the embryo. Finally, we identify nonimprinted genes that inherit promoter DNA methylation from parental gametes, suggesting that escape of post-fertilization DNA methylation reprogramming is prevalent in the mouse genome.


Genome Research | 2012

Global profiling of DNA methylation erasure in mouse primordial germ cells

Sylvain Guibert; Thierry Forné; Michael Weber

Epigenetic reprogramming, characterized by loss of cytosine methylation and histone modifications, occurs during mammalian development in primordial germ cells (PGCs), yet the targets and kinetics of this process are poorly characterized. Here we provide a map of cytosine methylation on a large portion of the genome in developing male and female PGCs isolated from mouse embryos. We show that DNA methylation erasure is global and affects genes of various biological functions. We also reveal complex kinetics of demethylation that are initiated at most genes in early PGC precursors around embryonic day 8.0-9.0. In addition, besides intracisternal A-particles (IAPs), we identify rare LTR-ERV1 retroelements and single-copy sequences that resist global methylation erasure in PGCs as well as in preimplantation embryos. Our data provide important insights into the targets and dynamics of DNA methylation reprogramming in mammalian germ cells.


Current Topics in Developmental Biology | 2013

Functions of DNA methylation and hydroxymethylation in mammalian development.

Sylvain Guibert; Michael Weber

DNA methylation occurs at cytosines, predominantly in the CpG dinucleotide context and is a key epigenetic regulator of embryogenesis and stem-cell differentiation in mammals. The genomic patterns of 5-methylcytosine are extensively reprogrammed during early embryonic development as well as in the germ-cell lineage. Thanks to improvements in high-throughput mapping technologies, it is now possible to characterize the dynamics of this epigenetic mark at the genome scale. DNA methylation plays multiple roles during development and serves to establish long-term gene silencing. In 2009, it was revealed that 5-hydroxymethylcytosine (5hmC) is another prominent cytosine modification catalyzed by the enzymes of the TET family and abundant in certain cell types. 5hmC has been thought to serve as an intermediate in the reaction of DNA demethylation or act as a signal for chromatin factors. Here, we review the current knowledge on the roles of these DNA epigenetic marks in development, epigenetic reprogramming, and pluripotency.


Nature Communications | 2015

Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency

Hongwei Chen; Irene Aksoy; Fabrice Gonnot; Pierre Osteil; Maxime Aubry; Claire Hamela; Cloé Rognard; Arnaud Hochard; Sophie Voisin; Emeline Fontaine; Magali Mure; Marielle Afanassieff; Elouan Cleroux; Sylvain Guibert; Jiaxuan Chen; Céline Vallot; Hervé Acloque; Clémence Genthon; Cécile Donnadieu; John De Vos; Damien Sanlaville; Jean François Guérin; Michael Weber; Lawrence W. Stanton; Claire Rougeulle; Bertrand Pain; Pierre-Yves Bourillot; Pierre Savatier

Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state characterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs. Together, these results show that temporarily increasing STAT3 activity is sufficient to reprogramme human PSCs to naive-like pluripotent cells.


Genome Biology | 2014

Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse

Ghislain Auclair; Sylvain Guibert; Ambre Bender; Michael Weber

BackgroundIn the mouse, the patterns of DNA methylation are established during early embryonic development in the epiblast. We quantified the targets and kinetics of DNA methylation acquisition in epiblast cells, and determined the contribution of the de novo methyltransferases DNMT3A and DNMT3B to this process.ResultsWe generated single-base maps of DNA methylation from the blastocyst to post-implantation stages and in embryos lacking DNMT3A or DNMT3B activity. DNA methylation is established within two days of implantation between embryonic days 4.5 and 6.5. The kinetics of de novo methylation are uniform throughout the genome, suggesting a random mechanism of deposition. In contrast, many CpG islands acquire methylation slowly in late epiblast cells. Five percent of CpG islands gain methylation and are found in the promoters of germline genes and in exons of important developmental genes. The onset of global methylation correlates with the upregulation of Dnmt3a/b genes in the early epiblast. DNMT3A and DNMT3B act redundantly to methylate the bulk genome and repetitive elements, whereas DNMT3B has a prominent role in the methylation of CpG islands on autosomes and the X chromosome. Reduced CpG island methylation in Dnmt3b-deficient embryos correlates with gene reactivation in promoters but reduced transcript abundance in gene bodies. Finally, DNMT3B establishes secondary methylation marks at imprinted loci, which distinguishes bona fide germline from somatic methylation imprints.ConclusionsWe reveal that the DNMT3 de novo methyltransferases play both redundant and specific functions in the establishment of DNA methylation in the mouse embryo.


Epigenomics | 2009

Dynamic regulation of DNA methylation during mammalian development.

Sylvain Guibert; Thierry Forné; Michael Weber

DNA methylation occurs on cytosines, is catalyzed by DNA methyltransferases (DNMTs), and is present at high levels in all vertebrates. DNA methylation plays essential roles in maintaining genome integrity, but its implication in orchestrating gene-expression patterns remained a matter of debate for a long time. Recent efforts to map DNA methylation at the genome level helped to get a better picture of the distribution of this mark and revealed that DNA methylation is more dynamic between cell types than previously anticipated. In particular, these datasets showed that DNA methylation is targeted to important developmental genes and might act as a barrier to prevent accidental cellular reprogramming. In this review, we will discuss the distribution and function of DNA methylation in mammalian genomes, with particular emphasis on the waves of global DNA methylation reprogramming occurring in early embryos and primordial germ cells.


PLOS ONE | 2015

Exposure to Endocrine Disruptor Induces Transgenerational Epigenetic Deregulation of MicroRNAs in Primordial Germ Cells

Miguel A. Brieño-Enríquez; Jesús García-López; David B. Cárdenas; Sylvain Guibert; Elouan Cleroux; Lukáš Děd; Juan de Dios Hourcade; Jana Pěknicová; Michael Weber; Jesús del Mazo

In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs) during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.


Methods of Molecular Biology | 2012

Methylated DNA Immunoprecipitation (MeDIP) from Low Amounts of Cells

Julie Borgel; Sylvain Guibert; Michael Weber

Methylated DNA immunoprecipitation (MeDIP) is an immunocapturing approach for unbiased enrichment of DNA that is methylated on cytosines. The principle is that genomic DNA is randomly sheared by sonication and immunoprecipitated with an antibody that specifically recognizes 5-methylcytidine (5mC), which can be combined with PCR or high-throughput analysis (microarrays, deep sequencing). The MeDIP technique has been originally used to generate DNA methylation profiles on a genome scale in mammals and plants. Here we provide an optimized version of the MeDIP protocol suitable for low amounts of DNA, which can be used to study DNA methylation in cellular populations available in small quantities.


Genome Research | 2016

EHMT2 directs DNA methylation for efficient gene silencing in mouse embryos

Ghislain Auclair; Julie Borgel; Lionel A. Sanz; Judith Vallet; Sylvain Guibert; Michael Dumas; Patricia Cavelier; Michael Girardot; Thierry Forné; Robert Feil; Michael Weber

The extent to which histone modifying enzymes contribute to DNA methylation in mammals remains unclear. Previous studies suggested a link between the lysine methyltransferase EHMT2 (also known as G9A and KMT1C) and DNA methylation in the mouse. Here, we used a model of knockout mice to explore the role of EHMT2 in DNA methylation during mouse embryogenesis. The Ehmt2 gene is expressed in epiblast cells but is dispensable for global DNA methylation in embryogenesis. In contrast, EHMT2 regulates DNA methylation at specific sequences that include CpG-rich promoters of germline-specific genes. These loci are bound by EHMT2 in embryonic cells, are marked by H3K9 dimethylation, and have strongly reduced DNA methylation in Ehmt2(-/-) embryos. EHMT2 also plays a role in the maintenance of germline-derived DNA methylation at one imprinted locus, the Slc38a4 gene. Finally, we show that DNA methylation is instrumental for EHMT2-mediated gene silencing in embryogenesis. Our findings identify EHMT2 as a critical factor that facilitates repressive DNA methylation at specific genomic loci during mammalian development.


Genome Biology | 2016

Single-CpG resolution mapping of 5-hydroxymethylcytosine by chemical labeling and exonuclease digestion identifies evolutionarily unconserved CpGs as TET targets

Aurélien A. Sérandour; Stéphane Avner; Elise A. Mahé; Thierry Madigou; Sylvain Guibert; Michael Weber; Gilles Salbert

Conventional techniques for single-base resolution mapping of epigenetic modifications of DNA such as 5-hydroxymethylcytosine (5hmC) rely on the sequencing of bisulfite-modified DNA. Here we present an alternative approach called SCL-exo which combines selective chemical labeling (SCL) of 5hmC in genomic DNA with exonuclease (exo) digestion of the bead-trapped modified DNA molecules. Associated with a straightforward bioinformatic analysis, this new procedure provides an unbiased and fast method for mapping this epigenetic mark at high resolution. Implemented on mouse genomic DNA from in vitro-differentiated neural precursor cells, SCL-exo sheds light on an intrinsic lack of conservation of hydroxymethylated CpGs across vertebrates.

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Michael Weber

University of Strasbourg

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Thierry Forné

University of Montpellier

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Julie Borgel

University of Montpellier

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Elouan Cleroux

University of Strasbourg

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Ambre Bender

University of Strasbourg

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Clémence Genthon

Institut national de la recherche agronomique

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Cécile Donnadieu

Institut national de la recherche agronomique

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