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Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells

Nature Cell Biology volume 8, pages 623–630 (2006)Cite this article

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)1,2. This SET–PR domain protein can form complexes with various chromatin modifiers in a context-dependent manner3,4. 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 melanogaster5. 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 cells6. 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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Figure 1: Immunoprecipitated mouse Blimp1 complex exhibits an arginine methyltransferase activity.
Figure 2: Overlapping expression of Blimp1 and Prmt5 in germ cells leads to specific pattern of H2A/H4R3me.
Figure 3: In vivo identification of Blimp1–Prmt5 binding elements within the genomic locus of Dhx38.
Figure 4: Dhx38 expression is upregulated in germ cells following translocation of Blimp1 and Prmt5 from the nucleus to the cytoplasm, resulting in a decrease in the levels of H2A/H4R3me2s modification.
Figure 5: Analysis of Blimp1, Prmt5 and Dhx38 in pluripotent embryonic germ and embryonic carcinoma cells (a) Immunostaining for Blimp1, Prmt5 and Dhx38 was performed on embryonic germ (EG) cells.

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Acknowledgements

We are most grateful to M. E. T. Padilla for thoughtful discussions and also for advice concerning the ChIP cloning. We thank S.J. Jeffries for help with the bioinformatics and C. Lee for help with animals and dissection of embryos. We thank A. Brehm, K. Calame, W. Herr and T. Nakano for providing reagents; and L. Schaeffer and E. Goillot for critical reading of the manuscript. K.A. was a recipient of a Marie Curie (PRZ/OO4/RG32856) and a Newton Trust (PRZ/008/RG38647) fellowship, and U.C.L was supported by a Wellcome Trust PhD studentship. This work was funded by grants from the Cancer Research UK to T.K. and by the Wellcome Trust to M.A.S.

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  1. Katia Ancelin

    Present address: LBMC/UMR5161, Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364, LYON, Cedex 07, France

Authors and Affiliations

  1. Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

    Katia Ancelin, Ulrike C. Lange, Petra Hajkova, Andrew J. Bannister, Tony Kouzarides & M. Azim Surani

  2. Max-Planck-Institute of Immunobiology, Stuebeweg 51, Freiburg, 79108, Germany

    Robert Schneider

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Ancelin, K., Lange, U., Hajkova, P. et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol 8, 623–630 (2006). https://doi.org/10.1038/ncb1413

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