Yoshiyuki Seki

Kwansei Gakuin University · Department of Biomedical Chemistry

Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here,...

Ten-eleven translocation (TET) proteins oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). 5fC and 5caC can be excised and repaired by the base excision repair (BER) pathway, implicating 5mC oxidation in active DNA demethylation. Genome-wide DNA methylation is erased in the transi...

Specification of germ cell fate is fundamental in development and heredity. Recent evidence indicates that in mice, specification of primordial germ cells (PGCs), the common source of both oocytes and spermatozoa, occurs through the integration of three key events: repression of the somatic program, reacquisition of potential pluripotency and ensui...

Induction of mouse germ cells occurs from the proximal epiblast at around embryonic day (E) 7.0. These germ cells then migrate to, and enter the gonads at about E10.5 after which they undergo epigenetic reprogramming including erasure of parental imprints. However, the epigenetic properties acquired by nascent germ cells and the potential remodelin...

Gene regulatory networks underlying cellular pluripotency are controlled by a core circuitry of transcription factors in mammals, including POU5F1. However, the evolutionary origin and transformation of pluripotency-related transcriptional networks have not been elucidated in deuterostomes. PR domain-containing protein 14 (PRDM14) is specifically e...

The pluripotency-associated transcriptional network is regulated by a core circuitry of transcription factors. The PR domain-containing protein PRDM14 maintains pluripotency by activating and repressing transcription in a target gene-dependent manner. However, the mechanisms underlying dichotomic switching of PRDM14-mediated transcriptional control...

Cell-fate maintenance is important to preserve the variety of cell types that are essential for the formation and function of tissues. We previously showed that the acetylated histone-binding protein BET-1 maintains cell fate by recruiting the histone variant H2A.z. Here, we report that Caenorhabditis elegans TLK-1 and the histone H3 chaperone CAF1...

PR-domain containing protein 14 (PRDM14) is a site-specific DNA-binding protein and is required for establishment of pluripotency in embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. DNA methylation status is regulated by the balance between de novo methylation and passive/active demethylation, and global DNA hypomethylation is...

Germline cells are the sole source of the transmission of genetic and epigenetic information to the next generation. Epigenetic information is reprogrammed during germ cell development to reacquire cellular totipotency and prevent the accumulation of epimutations. In this review, we summarize epigenetic reprogramming, in particular, DNA demethylati...

Germline cells reprogramme extensive epigenetic modifications to ensure the cellular totipotency of subsequent generations and to prevent the accumulation of epimutations. Notably, primordial germ cells (PGCs) erase genome-wide DNA methylation and H3K9 dimethylation marks in a stepwise manner during migration and gonadal periods. In this study, we...

DNA methylation is a central epigenetic event that regulates cellular differentiation, reprogramming, and pathogenesis. Genome-wide DNA demethylation occurs in preimplantation embryos and in embryonic germ cell precursors called primordial germ cells (PGCs). We previously showed that Dppa3, also known as Stella and PGC7, protects the maternal genom...

We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic component of wound healing to the male F1 and F2 generations. Underlying this adaptation was less gener...

In mammals, germ cells undergo striking dynamic changes in DNA methylation during their development. However, the dynamics and mode of methylation are poorly understood for short interspersed elements (SINEs) dispersed throughout the genome. We investigated the DNA methylation status of mouse B1 SINEs in male germ cells at different developmental s...

Epigenetic modifications, including DNA methylation and histone modifications, confer variety and stability of gene expression, which ensure the generation and maintenance of numerous distinctive cell types during mammalian development and in adults. Recent studies have suggested that genome-wide changes of epigenetic modifications, referred to as...

Germ cell specification in mice, which generates primordial germ cells (PGCs), the common source of the oocytes and spermatozoa, from the epiblast, integrates three key events: repression of the somatic program, re-acquisition of potential pluripotency, and genome-wide epigenetic reprogramming. A PR-domain containing protein, Blimp1 (also known as...

We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (H3K9me2), and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re-establishment of potential totipotency in the germline. We here e...

Germ cells provide an enduring link between generations and therefore must possess the fundamental ability of reprogramming their genome to generate a totipotent state. We wish to understand the molecular basis of the unique properties of the mammalian germ line. Recently we identified Blimp1, a potent transcriptional repressor of a histone methylt...

Germ cell fate in mice is induced in proximal epiblast cells at Embryonic Day (E) 6.5 by signaling molecules. Prdm1(also known as Blimp1)-positive lineage-restricted precursors of primordial germ cells (PGCs) initiate the formation of a cluster that differentiates into Dppa3 (also known as stella)-positive PGCs from around E7.0 onwards in the extra...

Germ cells provide an enduring link between generations and therefore must possess the fundamental ability of reprogramming their genome to generate a totipotent state. We wish to understand the molecular basis of the unique properties of the mammalian germ line. Recently we identified Blimp1, a potent transcriptional repressor of a histone methylt...

Myeloid elf-1-like factor (MEF) or Elf4, which is a member of the ETS transcription factor family, up-regulates the basal expression of lysozyme gene in epithelial cells and is constitutively localized in the nucleus. The mammalian cell nucleus is organized into distinct nuclear domains or compartments that are essential for diverse physiological p...

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine expressed in the non-small lung carcinoma cells (NSCLC). However, transcriptional regulation of GM-CSF is not well characterized in NSCLC. In this study we found that two cis-acting ETS family consensus sites are important for transcriptional regulation of GM-CSF in A549 human...

Although X chromosome transfer experiments indicated that tumor suppressor genes are present on the X chromosome, they have not been previously identified. In this report, we show that the ETS transcription factor MEF (ELF4), which is located on chromosome Xq26.1, possesses tumor suppressive capability. MEF expression was up-regulated by 5-azacytid...

We previously indicated that myeloid elf-1-like factor (MEF) but not elf-1, specifically activated lysozyme gene expression in epithelial cells. MEF is highly homologous at the nucleotide and amino acid level, with elf-1 especially in the ETS domain. Here, we report the functional analysis of the nuclear localization and transactivation properties...