A5086065297- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- interferon and immune responses
- AI in cancer detection
- Sperm and Testicular Function
- RNA modifications and cancer
- Digital Imaging for Blood Diseases
- 3D Printing in Biomedical Research
- Ovarian function and disorders
- Pancreatic and Hepatic Oncology Research
- Genetics and Neurodevelopmental Disorders
- Cancer, Hypoxia, and Metabolism
- Cell Image Analysis Techniques
- Reproductive System and Pregnancy
- Hepatitis B Virus Studies
- Plant Virus Research Studies
- Cellular Mechanics and Interactions
- Animal Disease Management and Epidemiology
- Microfluidic and Bio-sensing Technologies
- MicroRNA in disease regulation
Asahikawa Medical University
2017-2024
Osaka University
2012-2024
Chubu University
2015-2020
Rakuno Gakuen University
2006-2016
National University Cancer Institute, Singapore
2012-2014
National University of Singapore
2012-2014
Kobe Medical Center
2010
Kyoto University
2002-2008
Hokkaido University
1993-2006
Nara Institute of Science and Technology
2006
Covalent modification of histone tails is crucial for transcriptional regulation, mitotic chromosomal condensation, and heterochromatin formation. Histone H3 lysine 9 (H3-K9) methylation catalyzed by the Suv39h family proteins essential establishing architecture pericentric heterochromatin. We recently identified a mammalian methyltransferase (HMTase), G9a, which has strong HMTase activity towards H3-K9 in vitro. To investigate vivo functions we generated G9a -deficient mice embryonic stem...
Histone H3 Lys 9 (H3-K9) methylation is a crucial epigenetic mark for transcriptional silencing. G9a the major mammalian H3-K9 methyltransferase that targets euchromatic regions and essential murine embryogenesis. There single G9a-related in mammals, called GLP/Eu-HMTase1. Here we show GLP also important of mouse euchromatin. GLP-deficiency led to embryonic lethality, severe reduction mono- dimethylation, induction Mage-a gene expression, HP1 relocalization stem cells, all which were...
Ovulation in the mouse and other mammals is controlled by hormones secreted hypothalamo-pituitary-ovarian axis. We describe anovulation infertility female mice lacking microRNAs miR-200b miR-429. Both miRNAs are strongly expressed pituitary gland, where they suppress expression of transcriptional repressor ZEB1. Eliminating these miRNAs, turn, inhibits luteinizing hormone (LH) synthesis repressing transcription its β-subunit gene, which leads to lowered serum LH concentration, an impaired...
Although it is known that OCT4–NANOG are required for maintenance of pluripotent cells in vitro, the upstream signals regulate this circuit during early development vivo have not been identified. Here we demonstrate, first time, signal transducers and activators transcription 3 (STAT3)-dependent regulation circuitry necessary to maintain inner cell mass (ICM), source vitro-derived embryonic stem (ESCs). We show STAT3 highly expressed mouse oocytes becomes phosphorylated translocates nucleus...
Post-translational histone modifications play key roles in gene regulation, development and differentiation, but their dynamics living organisms remain almost completely unknown. To address this problem, we developed a genetically encoded system for tracking by generating fluorescent modification-specific intracellular antibodies (mintbodies) that can be expressed vivo. demonstrate, an H3 lysine 9 acetylation specific mintbody (H3K9ac-mintbody) was engineered stably human cells. In good...
Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t essential for very early stages of spermatogenesis. gene deficiency leads to azoospermia because the loss haploid germ cells. When differentiating spermatogonia emerge normal spermatogenesis, appears replaces canonical proteins. Structural biochemical analyses reveal...
G9a is a SET-domain mammalian histone methyltransferase responsible for mono- and dimethylation of lysine 9 in H3 (H3K9) at euchromatic regions. Recently we reported that forms stoichiometric heteromeric complex with another SET-domain-containing molecule, GLP/Eu-HMTase1. Although GLP can independently methylate H3K9 vitro, G9a/GLP formation seems to be essential their function as vivo. To further elucidate how G9a/GLP-mediated methylation transcriptional regulation are controlled, purified...
Eukaryotic gene expression is regulated in the context of chromatin. Dynamic changes post-translational histone modification are thought to play key roles fundamental cellular functions such as regulation cell cycle, development, and differentiation. To elucidate relationship between modifications functions, it important monitor dynamics single living cells. A genetically encoded probe called mintbody (modification-specific intracellular antibody), which a single-chain variable fragment...
Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via recruitment methyltransferase Dnmt1 to sites. However, involvement deubiquitylating enzymes (DUBs) targeting ubiquitylated is largely unknown. With use Xenopus egg extracts, we demonstrate here that Usp7, ubiquitin carboxyl-terminal hydrolase, forms stable complex with and recruited sites during replication. Usp7 deubiquitylates vitro. Inhibition activity or its depletion extracts results...
Hypoxia promotes stem cell maintenance and tumor progression, but it remains unclear how regulates long-term adaptation toward these processes. We reveal a striking downregulation of the hypoxia-inducible histone H3 lysine 9 (H3K9) demethylase JMJD1A as hallmark clinical human germ cell-derived tumors, such seminomas, yolk sac embryonal carcinomas. Jmjd1a was not essential for self-renewal played crucial role suppressor in opposition to hypoxia-regulated oncogenic H3K9 methyltransferase G9a....
Recent studies reveal that the mechanical environment influences behavior and function of various types cells, including stem cells. However, signaling pathways involved in regulation cell properties remain largely unknown. Using polyacrylamide gels with varying Young's moduli as substrates, we demonstrate mouse embryonic cells (mESCs) are induced to differentiate on substrates defined elasticity, involving Src-ShcA-MAP kinase pathway. While dual inhibition mitogen-activated protein (MAP)...
In mammals, DNA is methylated at CpG sites, which play pivotal roles in gene silencing and chromatin organization. Furthermore, methylation undergoes dynamic changes during development, differentiation, pathological processes. The conventional methods represent snapshots; therefore, the dynamics of this marker within living organisms remains unclear. To track dynamics, we made a knockin mouse that expresses red fluorescent protein (RFP)-fused methyl-CpG-binding domain (MBD) from ROSA26 locus...
Chromatin reorganization is necessary for pluripotent stem cells, including embryonic cells (ESCs), to acquire lineage potential. However, it remains unclear how ESCs maintain their characteristic chromatin state appropriate gene expression upon differentiation. Here, we demonstrate that chromodomain helicase DNA-binding domain 2 (Chd2) required the differentiation potential of mouse ESCs. Chd2-depleted showed suppressed developmentally regulated genes and subsequent defects without...
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for adaptation cancer cells to hypoxic microenvironment solid tumors. Previously, we showed that loss-of-function hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, by which blockade leads a suppressive effect remain poorly understood. We show is highly expressed breast associated with poor patient prognosis, where it function as...
Osteoclasts are multinucleated, giant cells derived from myeloid progenitors. While receptor activator of NF-κB ligand (RANKL) stimulation is the primary driver osteoclast differentiation, additional signaling further contributes to maturation. Here, we demonstrate that immunoglobulin superfamily member 11 (IgSF11), whose expression increases during regulates differentiation through interaction with postsynaptic density protein 95 (PSD-95), a scaffold multiple domains. IgSF11 deficiency in...
The Polycomb repressive complex 2 (PRC2) is a multicomponent histone H3K27 methyltransferase complex, best known for silencing the Hox genes during embryonic development. Polycomb-like proteins PHF1, MTF2, and PHF19 are critical components of PRC2 by stimulating its catalytic activity in stem cells. Tudor domains PHF1/19 have been previously shown to be readers H3K36me3 vitro. However, some other studies suggest that PHF1 co-localize with H3K27me3 mark but not Here, we provide further...