Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

doi:10.1038/srep32932

Cited by 4 publications

(3 citation statements)

References 50 publications

(65 reference statements)

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“…As in C. elegans embryonic somatic cells, mammalian ES cells also repress expression of germline genes (Blaschke et al 2013). Mouse ES cells have been shown to lose repression of germline genes when H3K9me2 marking of those genes is compromised by either Vitamin C treatment or knock-down of Max (myc-associate factor X) (Blaschke et al 2013; Maeda et al 2013; Sekinaka et al 2016; Ebata et al 2017). The conservation of H3K9me2 on germline genes, and its role in repressing those genes in developing somatic lineages, may represent an ancient regulatory role for H3K9me2.…”

Section: Discussionmentioning

confidence: 99%

Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

et al. 2019

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Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three Caenorhabditis elegans synMuv B mutants, lin-15B , lin-35 , and lin-37 —all of which display ectopic expression of germline genes in the soma. LIN-35 and LIN-37 are members of the conserved DREAM complex. LIN-15B has been proposed to work with the DREAM complex but has not been shown biochemically to be a member of the complex. We found that, in wild-type worms, synMuv B target genes and germline genes are enriched for the repressive histone modification dimethylation of histone H3 on lysine 9 (H3K9me2) at their promoters. Genes with H3K9me2 promoter localization are evenly distributed across the autosomes, not biased toward autosomal arms, as are the broad H3K9me2 domains. Both synMuv B targets and germline genes display a dramatic reduction of H3K9me2 promoter localization in lin-15B mutants, but much weaker reduction in lin-35 and lin-37 mutants. This difference between lin-15B and DREAM complex mutants likely represents a difference in molecular function for these synMuv B proteins. In support of the pivotal role of H3K9me2 in regulation of germline genes by LIN-15B , global loss of H3K9me2 but not H3K9me3 results in phenotypes similar to synMuv B mutants, high-temperature larval arrest, and ectopic expression of germline genes in the soma. We propose that LIN-15B -driven enrichment of H3K9me2 at promoters of germline genes contributes to repression of those genes in somatic tissues.

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Section: Discussionmentioning

confidence: 99%

Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

et al. 2019

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“…Bisulfite sequencing analysis by Sanger sequencing was carried out as described previously [ 18 ]. Max -KD VV3 ESCs with a Vasa -Venus reporter or control ESCs (ESCs transfected with AllStars negative control siRNA) were cultured for approximately 72 h and sorted using an S3e cell sorter (Bio-Rad).…”

Section: Methodsmentioning

confidence: 99%

DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell–related genes in mouse embryonic stem cells

et al. 2018

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In embryonic stem cells (ESCs), the expression of development-related genes, including germ cell–related genes, is globally repressed. The transcription factor MAX represses germ cell–related gene expression in ESCs via PCGF6-polycomb repressive complex 1 (PRC1), which consists of several epigenetic factors. However, we predicted that MAX represses germ cell–related gene expression through several additional mechanisms because PCGF6-PRC1 regulates the expression of only a subset of genes repressed by MAX. Here, we report that MAX associated with DNA methyltransferases (DNMTs) and the histone methyltransferase SETDB1 cooperatively control germ cell–related gene expression in ESCs. Both DNA methylation and histone H3 lysine 9 tri-methylation of the promoter regions of several germ cell–related genes were not affected by knockout of the PRC1 components, indicating that the MAX-DNMT and MAX-SETDB1 pathways are independent of the PCGF6-PRC1 pathway. Our findings provide insights into our understanding of MAX-based repressive mechanisms of germ cell–related genes in ESCs.

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“…As reported in the previous section, its expression is epigenetically regulated by the DNA methylation of CpG islands present in its promoter region. Moreover, the fact that the first exon and intron of the gene are highly enriched in the active histone H3K4me3 mark and lack repressive H3K27me3 [ 84 ] suggests that promoter demethylation can rapidly lead to gene activation. The expression of the Dazl gene, however, might also depend on signals from the gonadal ridges, since in the absence of these, PGCs of both sexes were shown not to undergo gametogenesis and to retain their pre-gonadal characteristics [ 58 ].…”

Section: Molecules and Conditions For Meiotic Beginningmentioning

confidence: 99%

The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors

Farini

Felici

2022

IJMS

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Meiosis is the unique division of germ cells resulting in the recombination of the maternal and paternal genomes and the production of haploid gametes. In mammals, it begins during the fetal life in females and during puberty in males. In both cases, entering meiosis requires a timely switch from the mitotic to the meiotic cell cycle and the transition from a potential pluripotent status to meiotic differentiation. Revealing the molecular mechanisms underlying these interrelated processes represents the essence in understanding the beginning of meiosis. Meiosis facilitates diversity across individuals and acts as a fundamental driver of evolution. Major differences between sexes and among species complicate the understanding of how meiosis begins. Basic meiotic research is further hindered by a current lack of meiotic cell lines. This has been recently partly overcome with the use of primordial-germ-cell-like cells (PGCLCs) generated from pluripotent stem cells. Much of what we know about this process depends on data from model organisms, namely, the mouse; in mice, the process, however, appears to differ in many aspects from that in humans. Identifying the mechanisms and molecules controlling germ cells to enter meiosis has represented and still represents a major challenge for reproductive medicine. In fact, the proper execution of meiosis is essential for fertility, for maintaining the integrity of the genome, and for ensuring the normal development of the offspring. The main clinical consequences of meiotic defects are infertility and, probably, increased susceptibility to some types of germ-cell tumors. In the present work, we report and discuss data mainly concerning the beginning of meiosis in mammalian female germ cells, referring to such process in males only when pertinent. After a brief account of this process in mice and humans and an historical chronicle of the major hypotheses and progress in this topic, the most recent results are reviewed and discussed.

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Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

Cited by 4 publications

References 50 publications

Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

Repression of Germline Genes in Caenorhabditis elegans Somatic Tissues by H3K9 Dimethylation of Their Promoters

DNMTs and SETDB1 function as co-repressors in MAX-mediated repression of germ cell–related genes in mouse embryonic stem cells

The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors

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