A5044687220- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Retinoids in leukemia and cellular processes
- Animal Genetics and Reproduction
- RNA Research and Splicing
- T-cell and Retrovirus Studies
- Genetic Syndromes and Imprinting
- DNA Repair Mechanisms
- Pluripotent Stem Cells Research
- RNA modifications and cancer
- Cancer-related gene regulation
- Sexual Differentiation and Disorders
- Reproductive System and Pregnancy
- Prenatal Screening and Diagnostics
- Glutathione Transferases and Polymorphisms
- Animal Disease Management and Epidemiology
- Acute Myeloid Leukemia Research
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Vector-Borne Animal Diseases
Keio University
1993-2025
Cincinnati Children's Hospital Medical Center
2017-2025
Perinatal Institute
2021-2025
University of Tsukuba
2024
University of Cincinnati Medical Center
2017-2023
Tokyo University of Agriculture
2013-2019
Cedars-Sinai Medical Center
1992-1999
Saitama Cancer Center
1996-1998
Showa University
1991
Dynamic epigenetic reprogramming occurs during mammalian germ cell development, although the targets of this process, including DNA demethylation and de novo methylation, remain poorly understood. We performed genome-wide methylation analysis in male female mouse primordial cells at embryonic days 10.5, 13.5, 16.5 by whole-genome shotgun bisulfite sequencing. Our high-resolution methylome maps demonstrated gender-specific differences CpG gene-specific levels fetal germline progression. There...
Zygotic genome activation (ZGA) is a critical postfertilization step that promotes totipotency and allows different cell fates to emerge in the developing embryo. MERVL (murine endogenous retrovirus-L) transiently upregulated at two-cell stage during ZGA. Although expression widely used as marker of totipotency, role this retrotransposon mouse embryogenesis remains elusive. Here, we show full-length transcripts, but not encoded retroviral proteins, are essential for accurate regulation host...
Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are activated by a conserved homeodomain-containing transcription factor, DUX. However, Dux-knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven an unknown factor(s). Here, we present multiple lines evidence the multicopy homeobox gene, Obox4, encodes factor highly expressed...
De novo DNA methylation (DNAme) during mouse oogenesis occurs within transcribed regions enriched for H3K36me3. As many oocyte transcripts originate in long terminal repeats (LTRs), which are heterogeneous even between closely related mammals, we examined whether species-specific LTR-initiated transcription units (LITs) shape the methylome. Here identify thousands of syntenic mouse, rat, and human that show divergent DNAme associated with private LITs, initiate lineage-specific LTR...
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...
Abstract DNA methylation, repressive histone marks, and PIWI-interacting RNA (piRNA) are essential for the control of retrotransposon silencing in mammalian germline. However, it remains unknown how these epigenetic pathways crosstalk to ensure male Here, we show that UHRF1 is responsible cooperates with germ cells. Conditional loss postnatal cells causes hypomethylation, upregulation retrotransposons, activation a damage response, switches global chromatin status, leading complete...
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...
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...
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...
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 demonstrate there...
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 demonstrate there...
Abstract During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program established to ensure completion of prophase. Here, we identify protein complex that consists germ-cell-specific zinc-finger ZFP541 its interactor KCTD19 as key regulators mouse prophase progression. Our genetic study shows are co-expressed from pachytene onward play an essential role testis. Furthermore,...
Abstract Infertility occurs in 15% of couples worldwide. Recurrent implantation failure (RIF) is one the major problems vitro fertilization and embryo transfer (IVF–ET) programs, how to manage patients with RIF achieve successful pregnancy outcomes remains unresolved. Here, a uterine polycomb repressive complex 2 (PRC2)-regulated gene network was found control implantation. Our RNA-seq analyses human peri-implantation endometrium obtained from fertile controls revealed that PRC2 components,...
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...