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.
"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 . 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. "
"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). "
"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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