A5033322034- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Multiple Myeloma Research and Treatments
- Genomics and Chromatin Dynamics
- Sperm and Testicular Function
- Glycosylation and Glycoproteins Research
- Reproductive Biology and Fertility
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Lymphadenopathy Diagnosis and Analysis
- Ocular Diseases and Behçet’s Syndrome
- Chromosomal and Genetic Variations
- Systemic Lupus Erythematosus Research
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- DNA Repair Mechanisms
- Animal Genetics and Reproduction
- Cancer-related gene regulation
- Cancer Treatment and Pharmacology
- Renal and related cancers
- Nuclear Structure and Function
- Oil Palm Production and Sustainability
Harvard University
2018-2023
Brigham and Women's Hospital
2018-2023
Inserm
2013-2018
Institut pour l'avancée des biosciences
2013-2018
Université Grenoble Alpes
2013-2018
Centre National de la Recherche Scientifique
2017-2018
Institut de Biosciences et Biotechnologies
2017-2018
The University of Tokyo
2016
Université Joseph Fourier
2013-2014
Kagawa University
1994
The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental the life cycle, yet underlying molecular details remain obscure. Here we show that an essential step genome-wide incorporation TH2B, histone H2B variant hitherto unknown function. Using mouse models in which TH2B depleted or C-terminally modified, directs final transformation dissociating nucleosomes into protamine-packed structures. Depletion induces compensatory mechanisms permit removal by...
Nuclear protein in testis (Nut) is a universal oncogenic driver the highly aggressive NUT midline carcinoma, whose physiological function male germ cells has been unclear. Here we show that expression of Nut normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which essential for completion histone-to-protamine exchange. Accordingly, inactivation induces sterility with spermatogenesis arrest at...
Nuclear protein in testis (NUT) carcinoma (NC) is a rare, distinctly aggressive subtype of squamous defined by the presence NUT-fusion oncogenes resulting from chromosomal translocation. In most cases, NUT gene (NUTM1) fused to bromodomain containing 4 (BRD4) forming BRD4-NUT oncogene. Here, novel fusion partner was discovered using next-generation sequencing and FISH young patient with an undifferentiated malignant round cell tumor. Interestingly, identified involved ZNF592, zinc finger...
Protamines confer a compact structure to the genome of male gametes. Here, we find that somatic cells can be remodeled by transient expression protamine 1 (Prm1). Ectopically expressed Prm1 forms scattered foci in nuclei fibroblasts, which coalescence into spermatid-like structures, concomitant with loss histones and reprogramming barrier, H3 lysine 9 methylation. Protaminized injected enucleated oocytes efficiently underwent maternal histone TH2B exchange developed normal blastocyst stage...
Abstract We report here newly discovered O -linked-N-acetylglucosamine ( -GlcNAc) modification of histone H2A at Ser 40 (H2AS40Gc). The mouse genome contains 18 isoforms, which 13 have and the other five Ala . combination production monoclonal antibody mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that -GlcNAcylation is specific to isoforms. H2AS40Gc site in L1 loop structure where two molecules interact nucleosome....
Histone hyperacetylation is thought to drive the replacement of histones by transition proteins that occur in elongating spermatids (ElS) after a general shut down transcription. The molecular machineries underlying this histone remain still undefined. Here, we focused our attention on role Cbp and p300 preceding late-gene transcriptional activity ElS. A strategy was designed partially deplete These cells progressed normally through spermiogenesis showed normal removal. However, genome-wide...
Abstract NUT carcinoma (NC), characterized most commonly by the BRD4-NUTM1 fusion, is a rare, aggressive variant of squamous with no effective treatment. BRD4-NUT drives growth and maintains poorly differentiated state NC activating pro-growth genes such as MYC, through formation massive, hyperacetylated, superenhancer-like domains termed megadomains. BRD4-NUT–mediated hyperacetylation chromatin facilitated chromatin-targeting tandem bromodomains BRD4, combined NUT, which recruits histone...
The post-meiotic phase of spermatogenesis is characterised by a radical reorganization the chromatin, leading to its nucleosomal toroid transition. replacement histones with protamine gradual process regulated hierarchical translation repressed mRNAs following events: incorporation testis-specific histone variants and general hyperacetylation, bromodomain proteins, transition concluded on DNA. In this work, we tested whether induced expression human 1 (PR1) in sheep somatic cells could...
<p>Figure S1. Rationale and readout for the dCAS9-NUT chemical screen. Figure S2. IRBM6 is highly active in vitro vivo. S3. induces transcriptional programs leading to growth arrest differentiation NC. S4. treatment redistribution of BRD4-NUT H3K27ac.</p>
<p>Supplementary Methods</p>
<p>Supplemental Table</p>
<p>Supplemental Table</p>
<p>Supplementary Figure Legends 1-4</p>
<p>Supplemental Table</p>
<p>Figure S1. Rationale and readout for the dCAS9-NUT chemical screen. Figure S2. IRBM6 is highly active in vitro vivo. S3. induces transcriptional programs leading to growth arrest differentiation NC. S4. treatment redistribution of BRD4-NUT H3K27ac.</p>
<p>Supplementary Figure Legends 1-4</p>
<p>Supplementary Methods</p>
<p>Supplemental Table</p>
<p>Supplemental Table</p>