A5067770709- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA Research and Splicing
- Animal Genetics and Reproduction
- DNA and Nucleic Acid Chemistry
- Genetics and Neurodevelopmental Disorders
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- Plant Genetic and Mutation Studies
- Gender Studies in Language
- Microtubule and mitosis dynamics
- TGF-β signaling in diseases
- Histone Deacetylase Inhibitors Research
- Genetic Syndromes and Imprinting
- Skin Protection and Aging
- Carcinogens and Genotoxicity Assessment
Hamamatsu University School of Medicine
2014-2023
Wellcome/MRC Cambridge Stem Cell Institute
2011-2015
University of Cambridge
2011-2015
National Institute of Genetics
2004-2011
Research Organization of Information and Systems
2004-2011
Japan Science and Technology Agency
2004-2007
Institute of Genetics
2003
Chiba University
2000-2003
Tokyo Medical and Dental University
2003
TGFβ is involved in various biological processes, including development, differentiation, growth regulation, and epithelial-mesenchymal transition (EMT). In TGFβ/Smad signaling, receptor-activated Smad complexes activate or repress their target gene promoters. cofactors are a group of Smad-binding proteins that promote recruitment to these Long noncoding RNAs (lncRNA), which behave as cofactors, have thus far not been identified. Here, we characterize novel lncRNA EMT-associated induced by...
Expression of Xist, which triggers X inactivation, is negatively regulated in cis by an antisense gene, Tsix, transcribed along the entire Xist gene. We recently demonstrated that Tsix silences through modification chromatin structure promoter region. This finding prompted us to investigate role transcription across Tsix-mediated silencing. Here, we prematurely terminated before and addressed its effect on silencing mouse embryos. found although 93% region encoding was transcribed,...
X-inactivation in female mammals is triggered by the association of non-coding Xist RNA cis with X chromosome. Although it has been suggested that A-repeat located proximal part required for chromosomal silencing ES cells, its role mouse not yet addressed. Here, we deleted and studied effects on during embryogenesis. The deletion,when paternally transmitted, caused a failure imprinted extraembryonic tissues, demonstrating essential embryo. Unexpectedly, was lack rather than defect function...
Genomic imprinting regulates parental origin-dependent monoallelic gene expression. It is mediated by either germline differential methylation of DNA (canonical imprinting) or oocyte-derived H3K27me3 (noncanonical in mice. Depletion Eed, an essential component Polycomb repressive complex 2, results genome-wide loss oocytes, which causes noncanonical (LOI) embryos. Although Eed maternal KO (matKO) embryos show partial lethality after implantation, it unknown whether LOI itself contributes to...
Cyclin D1, an oncogenic G1 cyclin, and YB‐1, a transcription factor involved in cell growth, are both over‐expressed several human cancers. In lung cancer, the functional association between YB‐1 cyclin D1 has never been elucidated. this study, we show is of cancer. Depletion endogenous by siRNA inhibited progression phase down‐regulated protein mRNA levels cancer cells. Forced over‐expression with reporter plasmid increased luciferase activity, ChIP assay results showed bound to promoter....
In mammals, silencing of one the two X chromosomes in female cells compensates for different number between sexes. The noncoding Xist RNA initiates chromosome inactivation. spreads from its transcription site over territory and triggers formation a repressive chromatin domain. To understand localization we aimed to develop system investigating living cells. Here report successful visualization transgenically expressed MS2-tagged mouse embryonic stem Imaging during an entire cell cycle shows...
The noncoding Tsix RNA is an antisense repressor of Xist and regulates X inactivation in mice. essential for preventing the maternally inherited chromosome extraembryonic lineages where imprinted X-chromosome (XCI) occurs. Here we establish inducible expression system investigating function development. We show that has a clear functional window Within this window, can repress , which accompanied by DNA methylation promoter. As consequence repression, reactivation inactive (Xi) widely...
Abstract HBO1, a histone acetyl transferase, is co-activator of DNA pre-replication complex formation. We recently reported that HBO1 phosphorylated by ATM and/or ATR and binds to DDB2 after ultraviolet irradiation. Here, we show at cyclobutane pyrimidine dimer (CPD) sites mediates acetylation facilitate recruitment XPC the damaged sites. Furthermore, facilitates accumulation SNF2H ACF1, an ATP-dependent chromatin remodelling complex, CPD Depletion inhibited repair CPDs sensitized cells...
Proper development of T cells depends on lineage-specific regulators controlled transcriptionally and posttranslationally to ensure precise levels at appropriate times. Conditional inactivation F-box protein Fbw7 in mouse T-cell resulted reduced thymic CD4 single-positive (SP) splenic CD4(+) CD8(+) cell proportions. deficiency skewed CD8 SP lineage differentiation, which exhibited a higher incidence apoptosis. Similar perturbations during CD8-positive were reported with transgenic mice,...
Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone for forming the prereplicative complex (pre-RC) at replication origin. Pre-RC formation completed by loading of MCM2-7 heterohexameric complex, which functions as helicase in DNA replication. HBO1 recruited origin CDT1 acetylates H4 relax chromatin conformation and facilitates MCM onto origins. However, acetylation status mechanism regulation H3 origins remain elusive. positively regulates cell proliferation...
One of the two X chromosomes in female mammals is inactivated by noncoding Xist RNA. In mice, chromosome inactivation (XCI) regulated antisense RNA Tsix, which represses on active chromosome. absence PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) established over promoter. Simultaneous disruption Tsix and PRC2 leads to derepression turn silencing single male embryonic stem cells. Here, we identified 36 (H3K36me3) as a modification that recruited cotranscriptionally extends...
Recent studies have demonstrated that lysine acetylation of histones is crucial for nucleotide excision repair (NER) by relaxing the chromatin structure, which facilitates recruitment factors. However, few focused on contribution histone deacetylases (HDAC) to NER. Here, we found H3 Lys14 (H3K14) was deacetylated HDAC3 after UV irradiation. Depletion caused defects in cyclobutene pyrimidine dimer and sensitized cells HDAC3-depleted had impaired unscheduled DNA synthesis, but not recovery RNA...
X chromosome inactivation (X-inactivation) in female mammals is triggered by differential upregulation of the Xist gene on one two chromosomes and subsequent coating cis with its non-coding transcripts. Although targeted mutation has clearly shown that essential for X-inactivation cis, molecular mechanism which RNA induces silencing largely unknown. Here, we demonstrate an mutant generated previously mouse targeting, Xist(IVS), unique it partially retains capacity to silence chromosome....
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with poor prognosis and no curative therapies. SCF-Skp2 E3 ligase target for cancer therapy, but there have been reports about Skp2 as IPF. Here we demonstrate that promising therapeutic We examined whether disrupting suppressed in bleomycin (BLM)-induced mouse model found was significantly Skp2-deficient mice compared controls. The accumulation of fibrotic markers such collagen type 1 fibronectin BLM-infused decreased mice....
Differential induction of the X-linked non-coding <i>Xist</i> gene is a key event in process X inactivation occurring female mammalian embryos. negatively regulated <i>in cis</i> by its antisense <i>Tsix</i> through modification chromatin structure. The maternal allele, which normally silent extraembryonic lineages, ectopically activated when disrupted on same chromosome, and subsequently chromosome undergoes lineages even males. However, it still unknown...
The fine-scale dynamics from euchromatin (EC) to facultative heterochromatin (fHC) has remained largely unclear. Here, we focus on Xist and its silencing initiator Tsix as a paradigm of transcription-mediated conversion EC fHC. In mouse epiblast stem cells, induction recapitulates the at promoter. Investigating reveals that proceeds in stepwise manner. Initially, transient opened chromatin structure is observed. second step, gene initiated dependent Tsix, which reversible accompanied by...
One of the two X chromosomes becomes inactivated during early development female mammals. Recent studies demonstrate that inactive chromosome is rich in histone H3 methylated at Lys-9 and Lys-27, suggesting an important role for these modifications X-inactivation. It has been shown mouse Eed required maintenance X-inactivation extraembryonic lineages. Interestingly, associates with Ezh2 to form a complex possessing methyltransferase activity predominantly Lys-27. We previously showed G9a one...
Abstract The known oncogene cyclin D1 (CCND1) participates in progression of the cell cycle from G1 to S-phase. Expression is frequently promoted multiple human cancers including non–small lung cancer (NSCLC). However, a relationship between expression and prognosis NSCLC has not been confirmed. NKX2-1 homeobox transcription factor involved pulmonary development as differentiation-promoting factor. In NSCLC, it acts metastasis suppressor correlates with good prognosis. Here, NKX2-1–binding...