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Ancelin, K. et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat. Cell Biol. 8, 623-630

Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Nature Cell Biology (Impact Factor: 19.68). 07/2006; 8(6):623-30. DOI: 10.1038/ncb1413
Source: PubMed

ABSTRACT

Blimp1, a transcriptional repressor, has a crucial role in the specification of primordial germ cells (PGCs) in mice at embryonic day 7.5 (E7.5). This SET-PR domain protein can form complexes with various chromatin modifiers in a context-dependent manner. Here, we show that Blimp1 has a novel interaction with Prmt5, an arginine-specific histone methyltransferase, which mediates symmetrical dimethylation of arginine 3 on histone H2A and/or H4 tails (H2A/H4R3me2s). Prmt5 has been shown to associate with Tudor, a component of germ plasm in Drosophila melanogaster. Blimp1-Prmt5 colocalization results in high levels of H2A/H4 R3 methylation in PGCs at E8.5. However, at E11.5, Blimp1-Prmt5 translocates from the nucleus to the cytoplasm, resulting in the loss of H2A/H4 R3 methylation at the time of extensive epigenetic reprogramming of germ cells. Subsequently, Dhx38, a putative target of the Blimp1-Prmt5 complex, is upregulated. Interestingly, expression of Dhx38 is also seen in pluripotent embryonic germ cells that are derived from PGCs when Blimp1 expression is lost. Our study demonstrates that Blimp1 is involved in a novel transcriptional regulatory complex in the mouse germ-cell lineage.

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    • "Additionally, PRDM1 is essential for the maintenance of PRDM14 [3] [13]; therefore, the impaired Sox2 transcription in prdm1 -/-embryos probably resulted from low levels of PRDM14, rather than the absence of PRDM1. In migrating PGCs, PRDM1 also functions in a complex with TFAP2C or PRMT5 to repress some pluripotency genes with a role in preventing the PGCs from acquiring a pluripotent stem-cell-like phenotype [18] [19]. The tfap2c +/-male mice developed testicular tumors that resembled embryonal carcinoma cells as PGCs failed to downregulate pluripotency genes [19]. "
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    ABSTRACT: The process of germline development carries genetic information and preparatory totipotency across generations. The last decade witnessed remarkable successes in the generation of germline cells from mouse pluripotent stem cells, especially induced germline cells with the capacity for producing viable offspring, suggesting clinical applications of induced germline cells in humans. However, to date, the culture systems for germline induction with accurate sex-specific meiosis and epigenetic reprogramming have not been well-established. In this study, we primarily focus on the mouse model to discuss key signaling events for germline induction. We review mechanisms of competent regulators on primordial germ cell induction and discuss current achievements and difficulties in inducing sex-specific germline development. Furthermore, we review the developmental identities of mouse embryonic stem cells and epiblast stem cells under certain defined culture conditions as it relates to the differentiation process to become germline cells.
    Preview · Article · Dec 2015 · Biology of Reproduction
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    • "In mouse, interaction of blimp1 (Blymphocyte-induced maturation protein 1) with Prmt (histone methyltransferase) represses chromatin transcription and prevents trans-differentiation from germ cells to somatic cells. In the blimp1-knockout mouse, germ cells cannot form69707172. In the present study, a blimp1 (Unigene15201_All), three Prmt (PRMT2: Unige- ne7507_All, PRMT3: CL2301.Contig2_All, CL2301.Con- tig1_All, PRMT6: Unigene14757_All), and a chromatin target of Prmt1 protein genes (Unigene4147_All) were identified, indicating a similar regulation of germ cell fate at the transcriptional level in shrimp. "
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    ABSTRACT: Background: The Pacific white shrimp (Litopenaeus vannamei) is the world's most prevalent cultured crustacean species. However, the supply of high-quality broodstocks is limited and baseline information related to its reproductive activity and molecular issues related to gonad development are scarce. In this study, we performed transcriptome sequencing on the gonads of adult male and female L. vannamei to identify sex-related genes. Results: A total of 25.16 gigabases (Gb) of sequences were generated from four L. vannamei gonadal tissue libraries. After quality control, 24.11 Gb of clean reads were selected from the gonadal libraries. De-novo assembly of all the clean reads generated a total of 65,218 unigenes with a mean size of 1021 bp and a N50 of 2000 bp. A search of all-unigene against Nr, SwissProt, KEGG, COG and NT databases resulted in 26,482, 23,062, 20,659, 11,935 and 14,626 annotations, respectively, providing a total of 30,304 annotated unigenes. Among annotated unigenes, 12,320 unigenes were assigned to gene ontology categories and 20,659 unigenes were mapped to 258 KEGG pathways. By comparing the ovary and testis libraries, 19,279 testicular up-regulated and 3,529 ovarian up-regulated unigenes were identified. Enrichment analysis of differentially expressed unigenes resulted in 1060 significantly enriched GO terms and 34 significantly enriched KEGG pathways. Nine ovary-specific, 6 testis-specific, 45 testicular up-regulated and 39 ovarian up-regulated unigenes were then confirmed by semi-quantitative PCR and quantitative real-time PCR. In addition, using all-unigenes as a reference, a total of 13,233 simple sequence repeats (SSRs) were identified in 10,411 unigene sequences. Conclusions: The present study depicts the first large-scale RNA sequencing of shrimp gonads. We have identified many important sex-related functional genes, GO terms and pathways, all of which will facilitate future research into the reproductive biology of shrimp. We expect that the SSRs detected in this study can then be used as genetic markers for germplasm evaluation of breeding and imported populations.
    Full-text · Article · Nov 2015 · BMC Genomics
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    • "Another example is protein arginine methyltransferase 5 (PRMT5), a type II PRMT enzyme. This enzyme mediates the repression of a set of target genes with the transcriptional repressor B lymphocyte-induced maturation protein 1 (BLIMP1) by dimethylation of arginine 3 on histone H2A and/or H4 (H2A/H4R3me2s) in germ cells [11]. However, when the BLIMP1- Abbreviations: CRM1, chromosome region maintenance 1; EGFP, enhanced green fluorescent protein; H3K9, lysine 9 on histone H3; HMT, histone methyltransferase ; LMB, leptomycin B; mAb, monoclonal antibody; NES, nuclear export signal; NLS, nuclear localization signal; SETDB1, SET domain, bifurcated 1. * Corresponding authors. "
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    ABSTRACT: SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that methylates lysine 9 on histone H3. Although it is important to know the localization of proteins to elucidate their physiological function, little is known of the subcellular localization of human SETDB1. In the present study, to investigate the subcellular localization of hSETDB1, we established a human cell line constitutively expressing enhanced green fluorescent protein fused to hSETDB1. We then generated a monoclonal antibody against the hSETDB1 protein. Expression of both exogenous and endogenous hSETDB1 was observed mainly in the cytoplasm of various human cell lines. Combined treatment with the nuclear export inhibitor leptomycin B and the proteasome inhibitor MG132 led to the accumulation of hSETDB1 in the nucleus. These findings suggest that hSETDB1, localized in the nucleus, might undergo degradation by the proteasome and be exported to the cytosol, resulting in its detection mainly in the cytosol. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Aug 2015 · Biochemical and Biophysical Research Communications
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