A5050361720- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Chromosomal and Genetic Variations
- Prenatal Screening and Diagnostics
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Congenital heart defects research
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
- Immunodeficiency and Autoimmune Disorders
- Cancer-related Molecular Pathways
- Medical and Biological Sciences
- Nuclear Structure and Function
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- Science, Research, and Medicine
- Digestive system and related health
- Advanced biosensing and bioanalysis techniques
Max Planck Institute of Biochemistry
2019-2024
Austrian Academy of Sciences
2017-2023
Vienna Biocenter
2017-2023
Institute of Molecular Biotechnology
2017-2023
Max Planck Society
2023
Rockefeller University
2022
University of Oxford
2018
Medical Research Council
2004-2006
Hutchison/MRC Research Centre
2004-2006
Addenbrooke's Hospital
2005
Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and naïve paternal genome to generate totipotent embryo. Chromatin loops domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when how embryonic conformations are assembled. Here, we investigated whether mechanism cohesin-dependent loop extrusion generates structures within the one-cell Using snHi-C knockout embryos, demonstrate that...
Abstract Eukaryotic genomes are compacted into loops and topologically associating domains (TADs) 1–3 , which contribute to transcription, recombination genomic stability 4,5 . Cohesin extrudes DNA that thought lengthen until CTCF boundaries encountered 6–12 Little is known about whether loop extrusion impeded by DNA-bound machines. Here we show the minichromosome maintenance (MCM) complex a barrier restricts in G1 phase. Single-nucleus Hi-C (high-resolution chromosome conformation capture)...
Life begins with a switch in genetic control from the maternal to embryonic genome during zygotic activation (ZGA). Despite its importance, essential regulators of ZGA remain largely unknown mammals. On basis de novo motif searches, we identified orphan nuclear receptor Nr5a2 as key activator major mouse two-cell embryos. is required for progression beyond stage. It binds within SINE B1/Alu retrotransposable elements found cis-regulatory regions genes. Chemical inhibition suggests that 72%...
Gene expression during natural and induced reprogramming is controlled by pioneer transcription factors that initiate from closed chromatin. Nr5a2 a key factor regulates zygotic genome activation in totipotent embryos, pluripotency embryonic stem cells metabolism adult tissues, but the mechanism of its activity remains poorly understood. Here, we present cryo-electron microscopy structure human NR5A2 bound to nucleosome. The shows conserved carboxy-terminal extension (CTE) loop DNA-binding...
In multicellular eukaryotes, geminin prevents overreplication of DNA in proliferating cells. Here, we show that genetic ablation the mouse formation inner cell mass (ICM) and causes premature endoreduplication at eight cells, rather than 32 All cells geminin-deficient embryos commit to trophoblast lineage consist giant (TGCs) only. Geminin is also down-regulated TGCs wild-type blastocysts during S gap-like phases by proteasome-mediated degradation, suggesting loss part mechanism regulating...
The RASSF1A isoform of RASSF1 is frequently inactivated by epigenetic alterations in human cancers, but it remains unclear if and how acts as a tumor suppressor.RASSF1A overexpression reduces vitro colony formation the tumorigenicity cancer cell lines vivo.Conversely, knockdown causes multiple mitotic defects that may promote genomic instability.Here, we have used genetic approach to address function suppressor vivo targeted deletion Rassf1A mouse.Rassf1A null mice were viable fertile...
Abstract Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine normal and malignant tissue ( n = 67). Correlations with cell‐cycle parameters, pathological features, were then determined using an invasive carcinoma microarray 165). Breast carcinomas scanned for...
The frequency of egg aneuploidy and trisomic pregnancies increases with maternal age. To what extent individual approaches can delay the "maternal age effect" is unclear because multiple causes contribute to chromosomal abnormalities in mammalian eggs. We propose that ovulation determines physiological aging oocytes, a key aspect which ability accurately segregate chromosomes produce euploid test this hypothesis, ovulations were reduced using successive pregnancies, hormonal contraception,...
Cohesin is essential for genome folding and inheritance. In somatic cells, these functions are both mediated by Scc1-cohesin, which in mitosis released from chromosomes Wapl separase. mammalian oocytes, cohesion Rec8-cohesin. Scc1 expressed but neither required nor sufficient cohesion, its function remains unknown. Likewise, it unknown whether regulates one or cohesin complexes chromosome segregation mature oocytes. Here, we show that accurate meiosis I segregation, predominantly releases...
The genetic causes of primary antibody deficiencies and autism spectrum disorder (ASD) are largely unknown. Here, we report a patient with hypogammaglobulinemia ASD who carries biallelic mutations in the transcription factor PAX5. A patient-specific Pax5 mutant mouse revealed an early B cell developmental block impaired immune responses as cause hypogammaglobulinemia. mice displayed behavioral deficits all domains. model showed aberrant cerebellar foliation severely sensorimotor learning....
The pioneer transcription factor NR5A2 plays multiple roles in regulating zygotic genome activation and expression of lineage-determining during mouse pre-implantation development. However, how differentially regulates transcriptional networks at distinct developmental stages remains unknown. Here, we demonstrate the dynamics chromatin binding profiles from 2-cell to morula stage, which corresponds totipotency-to-pluripotency transition. Our CUT&Tag analysis identifies KLF GATA families...
Centrosome duplication like DNA replication must occur exactly once per cell cycle to maintain genomic stability. Cell fusion and microinjection assays gave rise the concept of “licensing” uncovered nuclear-intrinsic blocks over-replication recently also centrosome-intrinsic overduplication. The chromatin licence has been defined in molecular terms as pre-replication complex (pre-RC) antagonised by its regulator geminin. Geminin prevents pre-RC assembly S G2 phases. However, mechanisms that...