A5007661469- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- Prenatal Screening and Diagnostics
- RNA Research and Splicing
- Cancer-related gene regulation
- Animal Genetics and Reproduction
- RNA modifications and cancer
- Birth, Development, and Health
- Renal and related cancers
- Genetic Syndromes and Imprinting
- Gestational Diabetes Research and Management
- RNA and protein synthesis mechanisms
- Nuclear physics research studies
- 3D Printing in Biomedical Research
- Pregnancy and preeclampsia studies
- Child Welfare and Adoption
- Histone Deacetylase Inhibitors Research
- Atomic and Molecular Physics
- Chromosomal and Genetic Variations
- Oral microbiology and periodontitis research
- Advanced Chemical Physics Studies
Novo Nordisk Foundation
2020-2025
University of Copenhagen
1966-2025
Inserm
2018-2021
Centre National de la Recherche Scientifique
2018-2021
University of Cambridge
2012-2021
Institut Curie
2018-2021
Université Paris Sciences et Lettres
2018-2021
Sorbonne Université
2018-2020
Wellcome/MRC Cambridge Stem Cell Institute
2012-2018
Medical Research Council
2012-2018
Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion 5-hydroxymethylcytosine (5hmC), driven by high levels TET1 TET2. Global 5hmC initiates asynchronously among at embryonic day (E) 9.5 E10.5 accounts unique process imprint erasure. Mechanistically, enrichment is followed its protracted decline thereafter a rate...
Primordial germ cells (PGCs) and preimplantation embryos undergo epigenetic reprogramming, which includes comprehensive DNA demethylation. We found that PRMT5, an arginine methyltransferase, translocates from the cytoplasm to nucleus during this process. Here we show conditional loss of PRMT5 in early PGCs causes complete male female sterility, preceded by upregulation LINE1 IAP transposons as well activation a damage response. Similarly, maternal-zygotic also leads upregulation. is...
Xist RNA has been established as the master regulator of X-chromosome inactivation (XCI) in female eutherian mammals, but its mechanism action remains unclear. By creating novel Xist-inducible mutants at endogenous locus male mouse embryonic stem (ES) cells, we dissect role conserved A-B-C-F repeats initiation XCI. We find that transcriptional silencing can be largely uncoupled from Polycomb repressive complex 1 and 2 (PRC1/2) recruitment, which requires B C repeats. ΔB+C specifically loses...
Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 crucial postimplantation development, and coincides with redistribution enhancer zeste homolog 2 (EZH2)-dependent 27 trimethylation (H3K27me3). Loss G9a or EZH2 results upregulation distinct gene sets involved cell cycle regulation, germline...
The maternal-to-zygotic transition (MZT) marks the period when embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at 2-cell stage mice. We investigated function maternally factor Stella (encoded by Dppa3) using single-cell/embryo approaches. show that loss maternal results widespread transcriptional mis-regulation partial failure MZT. Strikingly, activation endogenous...
Abstract During X chromosome inactivation (XCI), in female placental mammals, gene silencing is initiated by the Xist long non‐coding RNA. accumulation at leads to enrichment of specific chromatin marks, including PRC2‐dependent H3K27me3 and SETD8‐dependent H4K20me1. However, dynamics this process relation RNA remains unknown as involvement H4K20me1 initiating silencing. To follow XCI living cells, we developed a genetically encoded, H3K27me3‐specific intracellular antibody or...
Conventional human pluripotent stem cells (hPSCs) are widely used to study early embryonic development, generate somatic cells, and model diseases, with differentiation potential aligned a post-implantation epiblast identity. In the past decade, naive hPSCs, representing pre-implantation stage, have been derived. Naive hPSCs efficiently differentiate towards extraembryonic lineages such as trophectoderm, primitive endoderm, mesoderm, also self-organize into blastocyst-like structures called...
Abstract Objective The obesity epidemic, driven by a complex interplay of environmental and biological factors, remains significant global health challenge. Herein, we investigate the impact food insecurity, characterized unpredictable access, on regulation body weight composition in mice. Methods Male female C57BL/6J mice were subjected to combination intermittent fasting calorie restriction simulate insecurity. Results Our new model demonstrates that insecurity increases fat mass decreases...
PorT is a membrane-associated protein shown to be essential for the maturation and secretion of class cysteine proteinases, gingipains, from periodontal pathogen Porphyromonas gingivalis . It was previously reported that located on periplasmic surface inner membrane function as chaperone maturing proteinases. Our modelling suggested it an integral outer-membrane with eight anti-parallel, membrane-traversing β -strands. In this report, localization model confirmed by structural functional...
Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role post-implantation (Zylicz et al., 2015). Here explore the impact of depleting maternally inherited G9a oocytes on shortly after fertilisation. We show that accumulates typically at 4 to 8 cell stage promote timely repression a subset stage-specific genes. Loss maternal inheritance...
<title>Abstract</title> Development is driven by a sequence of molecularly interconnected transcriptional, epigenetic, and metabolic changes. Specific metabolites, like α-ketoglutarate (αKG), function as signalling molecules affecting the activity chromatin modifying enzymes. It remains unclear, how such non-canonical metabolism coordinates specific cell-state changes especially in early development. Here we uncover that when naive human embryonic stem cells (nESC) are induced towards...
Abstract Xist RNA has been established as the master regulator of X-chromosome inactivation (XCI) in female eutherian mammals but its mechanism action remains unclear. By creating novel mutants at endogenous locus mouse embryonic stem (ES) cells, we dissect role conserved A-B-C-F repeats. We find that transcriptional silencing can be largely uncoupled from Polycomb repressive complex 1 and 2 (PRC1/2) recruitment, which requires repeats B C. ΔB+C specifically loses interaction with PCGF3/5...