title: Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells.
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.
authors.affiliation: Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Katia
authors.initials: K
authors.lastname: Ancelin
authors.forename: Ulrike C
authors.initials: UC
authors.lastname: Lange
authors.forename: Petra
authors.initials: P
authors.lastname: Hajkova
authors.forename: Robert
authors.initials: R
authors.lastname: Schneider
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Bannister
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
authors.forename: M Azim
authors.initials: MA
authors.lastname: Surani
mesh_terms: D021581:Active Transport, Cell Nucleus; D000251:Adenosine Triphosphatases / Q000235:genetics; D000367:Age Factors; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D006657:Histones; C513258:Prdm1 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D001120:Arginine; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011496:Protein Methyltransferases; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; D000251:Adenosine Triphosphatases