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


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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    • "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.
    Biochemical and Biophysical Research Communications 08/2015; 465(4). DOI:10.1016/j.bbrc.2015.08.065 · 2.30 Impact Factor
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    • "Prmt5 knockout mice die between E3.5 and E6.5, suggesting that Prmt5 plays essential role(s) in mammalian development, one of which appears to be maintaining of stem cell pluripotency (Tee et al., 2010). In association with Prdm1, Prmt5 is essential for the development of mouse primordial germ cells (Ancelin et al., 2006). In complex with Prdm4, Prmt5 maintains stem cell like properties of the neural stem cells (Chittka et al., 2012). "
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    ABSTRACT: Prdm1 is a global repressor of transcription that plays multiple important roles during embryonic development, including neural crest specification. Prdm1 acts by repressing large sets of genes via sequence-specific recruitment of co-repressors, many of which are epigenetic modifiers. It is not known whether Prdm1 is expressed during neural crest development in chick embryo. Moreover, the mechanism of Prdm1 action or the nature of possible binding partners that mediate its effects in the neural crest had not yet been addressed. Prdm1 binding partners are known to play important roles during embryonic development, yet in many cases no spatiotemporal expression analysis during early vertebrate development has been performed. In this paper we report the expression patterns of Prdm1 and seven of its known or putative binding partners (Hdac1 and 2, Tle1 and 3, G9a, Prmt5, Lsd1) during early stages of chicken embryogenesis. Prdm1 is expressed in the neural plate border and premigratory neural crest during chick development. Six Prdm1 binding partners (except Tle1) are co-expressed with Prdm1 in the prospective neural plate border at HH4-HH6, and all seven show strong and specific expression in the neural plate border at HH7-HH8, suggesting all of them may cooperate with Prdm1 during neural crest development in chick embryos. Copyright © 2014. Published by Elsevier B.V.
    Gene Expression Patterns 02/2015; 17(1). DOI:10.1016/j.gep.2014.12.003 · 1.38 Impact Factor
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    • "This is based on knockout (KO) experiments of the Drosophila Prmt5 homologue (dart5), which leads to infertility (Anne et al, 2007). In the mouse, PRMT5 has been hypothesised to induce germline fate as an interactor of BLIMP1 (Ancelin et al, 2006). A Prmt5 KO in the mouse results in early embryonic lethality (Tee et al, 2010); therefore , the new investigations made use of conditional deletion of the gene during PGC formation. "
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    ABSTRACT: Primordial germ cells (PGCs) are the embryonic precursors of the germ cell lineage that form sperm and egg cells. It is of great importance to preserve the germline from DNA damage and potentially from epimutations in order to ensure the survival of future generations. Recent research highlights the role of the protein arginine methyltransferase 5 (PRMT5) as an important player in DNA protection during germline development in the mouse (Kim et al, & Li et al,). Protecting the genetic integrity of the germline is of outmost importance. Two novel studies establish multiple roles of PRMT5 in safe-guarding genomic integrity of PGCs, beyond earlier proposed roles in the induction of germline fate. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
    The EMBO Journal 02/2015; 34(6). DOI:10.15252/embj.201591054 · 10.43 Impact Factor
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