A5064054309- Epigenetics and DNA Methylation
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Sperm and Testicular Function
- Genetics and Neurodevelopmental Disorders
- Sexual Differentiation and Disorders
- RNA modifications and cancer
- Hepatitis B Virus Studies
- Pancreatic and Hepatic Oncology Research
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Biotin and Related Studies
- Environmental Toxicology and Ecotoxicology
- Pesticide Exposure and Toxicity
- PARP inhibition in cancer therapy
- Gear and Bearing Dynamics Analysis
- Cancer-related Molecular Pathways
- Heat shock proteins research
- Cancer-related gene regulation
- Viral gastroenteritis research and epidemiology
- Lipid Membrane Structure and Behavior
Institute for Basic Science
2017-2024
University of Cambridge
2009-2017
Wellcome/Cancer Research UK Gurdon Institute
2012-2017
Wellcome Trust
2012-2017
Medical Research Council
2013-2014
Wellcome/MRC Cambridge Stem Cell Institute
2014
Seoul National University
1999-2012
University of Minnesota
2003-2009
Masonic Cancer Center
2009
Dmrt1 (doublesex and mab-3 related transcription factor 1) is a conserved transcriptional regulator of male differentiation required for testicular development in vertebrates. Here, we show that mice the 129Sv strain, loss causes high incidence teratomas, whereas these tumors do not form mutant C57BL/6J mice. Conditional gene targeting indicates fetal germ cells but Sertoli to prevent teratoma formation. Mutant undergo apparently normal up embryonic day 13.5 (E13.5), some fail arrest mitosis...
Primordial germ cells (PGCs) and somatic originate from postimplantation epiblast in mice. As pluripotency is lost upon differentiation of lineages, a naive epigenome the network are re‐established during PGC development. Here we demonstrate that Prdm14 contributes not only to specification, but also embryonic stem (ES) by repressing DNA methylation machinery fibroblast growth factor (FGF) signalling. This indicates critical role for programming PGCs promoting ES cells.
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...
Naive hypomethylated embryonic pluripotent stem cells (ESCs) are developmentally closest to the preimplantation epiblast of blastocysts, with potential contribute all tissues and germline, excepting extra-embryonic in chimeric embryos. By contrast, (EpiSCs) resembling postimplantation relatively more methylated show a limited for chimerism. Here, first time, we reveal advanced (ASCs), which beyond inner cell mass but higher potency than EpiSCs. Accordingly, single ASC contributes very...
Gametogenesis is a sexually dimorphic process requiring profound differences in germ cell differentiation between the sexes. In mammals, presence of heteromorphic sex chromosomes males creates additional sex-specific challenges, including incomplete X and Y pairing during meiotic prophase. This triggers formation heterochromatin domain, XY body. The body disassembles after prophase, but specialized chromatin persists, with further modification, through meiosis. Here, we investigate function...
Abstract Germ-line hypomorphism of the pleiotropic transcription factor Myc in mice, either through gene haploinsufficiency or deletion enhancers, delays onset various cancers while mice remain viable and exhibit only relatively mild pathologies. Using a genetically engineered mouse model which expression may be systemically reversibly hypomorphed at will, we asked whether this resistance to tumour progression is also emplaced when acutely imposed adult mice. Indeed, profoundly blocked KRas...
Blimp1 (Prdm1), the key determinant of primordial germ cells (PGCs), plays a combinatorial role with Prdm14 during PGC specification from postimplantation epiblast cells. They together initiate epigenetic reprogramming in early toward an underlying pluripotent state, which is equivalent to embryonic stem (ESCs). Whereas alone can promote and important for propagation it not known whether similarly involved. By using genetic approach, we demonstrate that dispensable derivation maintenance...
Centrosomes are the primary microtubule-organizing centers that important for mitotic spindle assembly. Centrosome amplification is commonly observed in human cancer cells and contributes to genomic instability. However, it not clear how centrosome duplication dysregulated cells. Here, we report ATAD5, a replisome protein unloads PCNA from chromatin as replication factor C-like complex (RLC), plays an role regulating duplication. ATAD5 present at centrosome, specifically base of mother...
Thyroid hormone receptor-interacting protein 13 (TRIP13) participates in various regulatory steps related to the cell cycle, such as mitotic spindle assembly checkpoint and meiotic recombination, possibly by interacting with members of HORMA domain family. Recently, it was reported that TRIP13 could regulate choice DNA repair pathway, i.e., homologous recombination (HR) or nonhomologous end-joining (NHEJ). However, is recruited damage sites within a few seconds after may therefore have...
Abstract: Gaegurin 4 (GGN4) is an antimicrobial peptide of 37 amino acids isolated from the skin a frog, Rana rugosa . GGN4 has disulfide bond between residues 31 and 37, which highly conserved among peptides genus, However, role this C‐terminal heptapeptide motif not well understood. In work, we compared membrane effects full‐length (C37) 1‐30 (C30), devoid seven to elucidate function motif. C37 induced significantly larger conductance (>10×) in model lipid bilayers formed with acidic...
There are hundreds of copies rDNA repeats in mammalian chromosomes and the ratio active, poised, or inactive is regulated epigenetic manners. Recent studies demonstrated that a post-DNA replication repair enzyme, SHPRH affects rRNA transcription by recognizing markers on promoters unveiled potential links between DNA ribosome biogenesis. This study suggests could be link mTOR-mediated regulations transcription, while concomitantly affecting genomic integrity.
Ubiquitination status of proliferating cell nuclear antigen (PCNA) is crucial for regulating DNA lesion bypass. After the resolution fork stalling, PCNA subsequently deubiquitinated, but underlying mechanism remains undefined. We found that N-terminal domain ATAD5 (ATAD5-N), largest subunit PCNA-unloading complex, functions as a scaffold Ub–PCNA deubiquitination. recognizes DNA-loaded through distinct DNA-binding and PCNA-binding motifs. Furthermore, forms heterotrimeric complex with...
Mammalian primordial germ cells (PGCs) are specified in the early post-implantation embryo. Attempts have been made to establish vitro PGC development since derivation of embryonic stem (ESCs) from blastocysts. Despite advances with mouse models, similar studies human cell not progressed because practical and ethical reasons prevent use embryos. Recently, we others developed a robust system for producing cell-like (hPGCLCs) ESCs induced pluripotent (iPSCs) by inducing competency cells....