A5057152082- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Sperm and Testicular Function
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Ubiquitin and proteasome pathways
- Reproductive Biology and Fertility
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Renal and related cancers
- Neurobiology and Insect Physiology Research
- Cancer-related gene regulation
- Insect and Arachnid Ecology and Behavior
- Genetics and Neurodevelopmental Disorders
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Animal Behavior and Reproduction
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Methemoglobinemia and Tumor Lysis Syndrome
- Fungal and yeast genetics research
- Pancreatic function and diabetes
Tokyo University of Science
2009-2025
Cincinnati Children's Hospital Medical Center
2015-2025
University of Cincinnati Medical Center
2015-2023
Azabu University
2018-2023
Institute for Reproductive Health
2016
During spermatogenesis, germ cells undergo massive cellular reconstruction and dynamic chromatin remodeling to facilitate highly diverse transcriptomes, which are required for the production of functional sperm. However, it remains unknown how germline is organized promote dynamic, complex transcriptomes spermatogenesis. Here, using ATAC-seq, we establish varied landscape open during We identify reorganization accessible in intergenic intronic regions mitosis-to-meiosis transition....
Significance The germline is responsible for the reproduction of an entire organism through recovery totipotency after fertilization. This ability presumably associated with a chromatin feature known as bivalent domains, which are marked both repressive and active histone modifications. In this study, we determine identity domain genes in male mice regulatory mechanism these genes. We demonstrate that SCML2 facilitates modification, H3K27me3, thereby establishing domains germline. Our study...
During spermatogenesis, a large number of germline genes essential for male fertility are coordinately activated. However, it remains unknown how timely activation this group is accomplished. Here we show that Polycomb-repressive complex 1 (PRC1) directs during spermatogenesis. Inactivation PRC1 in germ cells results the gradual loss stem cell population and severe differentiation defects, leading to infertility. In population, RNF2, dominant catalytic subunit PRC1, activates transcription...
The sex chromosomes are enriched with germline genes that activated during the late stages of spermatogenesis. Due to meiotic chromosome inactivation (MSCI), these chromosome-linked must escape silencing for activation in spermatids, thereby ensuring their functions male reproduction. RNF8, a DNA damage response protein, and SCML2, germline-specific Polycomb two major, known regulators this process. Here, we show RNF8 SCML2 cooperate regulate ubiquitination meiosis, an early step establish...
Precise epigenetic regulation of the sex chromosomes is vital for male germline. Here, we analyze meiosis in eight mouse models deficient various DNA damage response (DDR) factors, including Fanconi anemia (FA) proteins. We reveal a network FA and DDR proteins which core factors FANCA, FANCB, FANCC are essential FANCD2 foci formation, whereas BRCA1 (FANCS), MDC1, RNF8 required BRCA2 (FANCD1) SLX4 (FANCP) accumulation on during meiosis. In addition, modulate distinct histone marks...
Abstract DNA methylation patterns are inherited from the parental germline to embryo. In mature sperm, sites of unmethylated tightly coupled histone retention at gene regulatory elements that implicated in paternal epigenetic inheritance. The timing and mechanism site-specific demethylation male currently remains unknown. Here, we perform genome-wide profiling during spermatogenesis by capturing methylated through interaction with a methyl-DNA binding protein domain (MBD). Our data...
Intercellular transmission of messenger RNA (mRNA) is being explored in mammalian species using immortal cell lines. Here, we uncover an intercellular mRNA transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic under condition impermissible hPSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis...
Abstract Spermatogonial stem cells balance self-renewal with differentiation and spermatogenesis to ensure continuous sperm production. Here, we identify roles for the transcription factor zinc finger BTB domain-containing protein 16 (ZBTB16; also known as promyelocytic leukemia (PLZF)) in juvenile mouse undifferentiated spermatogonia (uSPG) promoting cell-cycle progression maintain uSPG transit-amplifying states. Notably, ZBTB16, Spalt-like 4 (SALL4) SRY-box 3 (SOX3) colocalize at over...
As transposable elements (TEs) coevolved with the host genome, genome exploited TEs as functional regulatory of gene expression. Here we show that a subset KRAB domain–containing zinc-finger proteins (KZFPs), which are highly expressed in mitotically dividing spermatogonia, repress enhancer function endogenous retroviruses (ERVs) and release from KZFP-mediated repression allows activation ERV enhancers upon entry into meiosis. This feature is observed for independently evolved KZFPs ERVs...
Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular transfer phenomenon that allows for the adaptation and reprogramming human primed pluripotent stem cells (hPSCs). This process induced by direct contact-mediated coculture with mouse embryonic (mESCs) under condition impermissible PSC culture. Mouse-derived contents are transmitted into adapted hPSCs only coculture. Transfer-specific analysis show...
The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest oocytes residing primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies entry, but chromatin changes that underpin generation and preservation reserves are poorly defined. We report Polycomb Repressive Complex 1 (PRC1) establishes repressive states perinatal mouse directly suppress gene expression program prophase-I thereby...
Spermatogenesis involves the progressive reorganization of heterochromatin. However, mechanisms that underlie dynamic remodeling heterochromatin remain unknown. Here, we identify SCML2, a germline-specific Polycomb protein, as critical regulator organization in spermatogenesis. We show SCML2 accumulates on pericentromeric (PCH) male germ cells, where it suppresses PRC1-mediated monoubiquitylation histone H2A at Lysine 119 (H2AK119ub) and promotes deposition PRC2-mediated H3K27me3 during...
Abstract Sperm chromatin retains small amounts of histones, and states sperm mirror gene expression programs the next generation. However, it remains largely unknown how paternal epigenetic information is transmitted through chromatin. Here, we present a novel mouse model inheritance, in which deposition Polycomb repressive complex 2 (PRC2) mediated-repressive H3K27me3 attenuated germline. By applying modified methods assisted reproductive technology using testicular sperm, rescued...
TdT interacting factor 1 (TdIF1) was identified as a protein that binds to terminal deoxynucleotidyltransferase (TdT) negatively regulate activity. is template-independent DNA polymerase catalyzes the incorporation of deoxynucleotides 3'-hydroxyl end templates increase junctional diversity immunoglobulin or T-cell receptor (TcR) genes. Here, using bioinformatics analysis, we binding, binding and dimerization regions, nuclear localization signal (NLS) in TdIF1. TdIF1 bound double-stranded...
Bood POZ containing gene type 2 (BPOZ-2), which contains ankyrin repeats, NLS, BTB/POZ domains and LXXLL motifs, is an adaptor protein for the E3 ubiquitin ligase scaffold CUL3. We isolated a cDNA encoding eukaryotic elongation factor 1A1 (eEF1A1) as BPOZ-2 binding by screening human thymus library using yeast two-hybrid system. eEF1A1 essential translation also involved in 26S proteasome-dependent degradation of misfolded or unfolded proteins. The between was confirmed pull-down...
Abstract Spermatogonial stem cells functionality reside in the slow-cycling and heterogeneous undifferentiated spermatogonia cell population. This pool of supports lifelong fertility adult males by balancing self-renewal differentiation to produce haploid gametes. However, molecular mechanisms underpinning long-term stemness during adulthood remain unclear. Here, we discover that an epigenetic regulator, Polycomb repressive complex 1 (PRC1), shields from differentiation, maintains slow...
Terminal deoxynucleotidyltransferase (TdT) interacting factor 2 (TdIF2) is an acidic protein that binds to TdT. TdIF2 DNA and core histones contains acidic-amino acid-rich region in its C-terminus. It has therefore been suggested function as a histone chaperone within the nucleus. localized nucleolus HEK 293T cells, N-terminal (residues 1–234) C-terminal 606–756) regions were crucial for nucleolar localization. A chromatin immunoprecipitation (ChIP) assay showed associated with promoter of...
Mutations in the gene encoding bilirubin UDP-glucuronosyltransferase (UGT1A1) are known to cause Crigler-Najjar syndrome type II (CN-II). We previously encountered a patient with nonsense mutation (Q331X) on one allele and no other mutations promoter region or exons, proposed that CN-II is inherited as dominant trait due formation of heterologous subunit structure comprised altered UGT1A1 product (UGT1A1-p.Q331X) intact UGT1A1. Here, we investigated molecular basis this case by expressing...
Isolation of meiotic spermatocytes is essential to investigate molecular mechanisms underlying meiosis and spermatogenesis. Although there are established cell isolation protocols using Hoechst 33342 staining in combination with fluorescence-activated sorting, it requires sorters equipped an ultraviolet laser. Here we describe a protocol the DyeCycle Violet (DCV) stain, low cytotoxicity DNA binding dye structurally similar 33342. DCV can be excited by both violet lasers, which improves...