A5082449290- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- DNA Repair Mechanisms
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Genetics, Aging, and Longevity in Model Organisms
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Plant Molecular Biology Research
- Genetic Mapping and Diversity in Plants and Animals
- Bioinformatics and Genomic Networks
- Ubiquitin and proteasome pathways
- Invertebrate Immune Response Mechanisms
- Cancer Genomics and Diagnostics
- Neurobiology and Insect Physiology Research
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Gene Regulatory Network Analysis
The University of Tokyo
2016-2025
Tokyo University of Science
2024
Quantitative BioSciences
2019-2023
Japan Agency for Medical Research and Development
2019
Toyoda Gosei (Japan)
2013-2014
Japan Science and Technology Agency
2014
University of Nottingham
2013
Kyoto University
2007-2010
The structural maintenance of chromosomes (SMC) protein complexes—cohesin, condensin, and the Smc5/6 complex (Smc5/6)—are essential for chromosome function. At molecular level, these complexes fold DNA by loop extrusion. Accordingly, cohesin creates loops in interphase, condensin compacts mitotic chromosomes. However, role Smc5/6's recently discovered extrusion activity is unknown. Here, we uncover that associates with transcription-induced positively supercoiled at cohesin-dependent...
The initiation of human pregnancy is marked by the implantation an embryo into uterine environment; however, underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)–EMO, which emulate in vivo architecture tissue. AO-EMO comprise exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network. When cocultured with embryonic stem cell–derived blastoids,...
DNA unwinding at eukaryotic replication forks displaces parental histones, which must be redeposited onto nascent in order to preserve chromatin structure. By screening systematically for replisome components that pick up histones released from into a yeast cell extract, we found the Mcm2 helicase subunit binds cooperatively with FACT (facilitiates transcription) complex, helps re-establish during transcription. does not associate Mcm2-7 origins G1 phase but is subsequently incorporated...
Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase copy number during a synchronous S-phase allowed precise determination of genome replication. To map locations, forks were stalled close their initiation sites; therefore, enrichment was limited Replication timing profiles generated asynchronous cultures using...
The cohesin complex is crucial for chromosome segregation during mitosis and has recently also been implicated in transcriptional regulation chromatin architecture. NIPBL protein required the loading of onto chromatin, but how where loaded vertebrate cells unclear. Heterozygous mutations were found 50% cases Cornelia de Lange Syndrome (CdLS), a human developmental syndrome with phenotype. However, no defects mitotic function have observed so far links between are We show that binds to...
Abstract Chromosome condensation is a hallmark of mitosis in eukaryotes and prerequisite for faithful segregation genetic material to daughter cells. Here we show that condensin, which essential assembling condensed chromosomes, helps preclude the detrimental effects gene transcription on mitotic condensation. ChIP-seq profiling reveals fission yeast condensin preferentially binds active protein-coding genes transcription-dependent manner during mitosis. Pharmacological attenuation largely...
The sliding clamp PCNA is a crucial component of the DNA replication machinery. Timely loading and unloading are central for genome integrity must be strictly coordinated with other processing steps during replication. Here, we show that S. cerevisiae Elg1 factor C-like complex (Elg1-RLC) unloads genome-wide following Okazaki fragment ligation. In absence Elg1, retained on chromosomes in wake forks, rather than at specific sites. Degradation ligase Cdc9 leads to accumulation chromatin,...
Genome function depends on regulated chromosome folding, and loop extrusion by the protein complex cohesin is essential for this multilayered organization. The chromosomal positioning of controlled transcription, also localizes to stalled replication forks. However, role transcription in looping remains unclear. Here, we show that reduction chromosome-bound RNA polymerase weakens normal boundaries, allowing form new long-range cis interactions. Stress response genes induced inhibition are...
The cohesin complex, which is essential for sister chromatid cohesion and chromosome segregation, also inhibits resolution of intertwinings (SCIs) by the topoisomerase Top2. cohesin-related Smc5/6 complex (Smc5/6) instead accumulates on chromosomes after Top2 inactivation, known to lead a buildup unresolved SCIs. This suggests that can influence chromosomal association via its role in SCI protection. Using high-resolution ChIP-sequencing, we show localization budding yeast duplicated indeed...
Chromatin immunoprecipitation with high‐throughput sequencing (Ch IP ‐seq) can identify genomic regions that bind proteins involved in various chromosomal functions. Although the development of next‐generation sequencers offers technology needed to these protein‐binding sites, analysis be computationally challenging because data sometimes consist >100 million reads/sample. Herein, we describe a cost‐effective and time‐efficient protocol is generally applicable Ch ‐seq analysis; this uses...
Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on are poorly understood. Here, we show heat shock transcription factor (HSF1) recruits through scaffold protein PARP13. In response to damage, activated auto-poly-ADP-ribosylated dissociates from HSF1-PARP13, redistributes lesions damage-inducible gene loci. Histone deacetylase maintains ternary complex by inactivating...
NUP98 and NUP214 form chimeric fusion proteins that assemble into phase-separated nuclear bodies containing CRM1, a export receptor. However, these bodies' function in controlling gene expression remains elusive. Here, we demonstrate the of NUP98::HOXA9 SET::NUP214 promote condensation mixed lineage leukemia 1 (MLL1), histone methyltransferase essential for maintenance HOX expression. These are robustly associated with MLL1/CRM1 co-localized on chromatin. Furthermore, whole-genome...
In eukaryotes, the replication of chromosome DNA is coordinated by a timing program that temporally regulates firing individual origins. However, molecular mechanism underlying remains elusive. Here, we report telomere-binding protein Taz1 plays crucial role in control fission yeast. A element located proximal to late origin arm represses initiation from early S phase. Systematic deletion and substitution experiments demonstrated two tandem telomeric repeats are essential for this...
The structural maintenance of chromosomes (SMC) proteins constitute the core critical complexes involved in organization chromosomes. In yeast, Smc5/6 complex is known to mediate repair DNA breaks and replication repetitive genomic regions, including ribosomal loci telomeres. mammalian cells, which have diverse genome structure scale from has also been implicated damage response, but its further function unchallenged conditions remains elusive. this study, we addressed behavior during cell...