Germ cells are the only cells that transmit genetic information to the next generation, and they therefore must be prevented from differentiating inappropriately into somatic cells1. A common mechanism by which germline progenitors are protected from differentiation-inducing signals is a transient and global repression of RNA polymerase II (RNAPII)-dependent transcription1. In both Drosophila and Caenorhabditis elegans embryos, the repression of messenger RNA transcription during germ cell specification correlates with an absence of phosphorylation of Ser 2 residues in the carboxy-terminal domain of RNAPII (hereafter called CTD)2, a critical modification for transcriptional elongation3. Here we show that, in Drosophila embryos, a small protein encoded by polar granule component (pgc) is essential for repressing CTD Ser 2 phosphorylation in newly formed pole cells, the germline progenitors. Ectopic Pgc expression in somatic cells is sufficient to repress CTD Ser 2 phosphorylation. Furthermore, Pgc interacts, physically and genetically, with positive transcription elongation factor b (P-TEFb), the CTD Ser 2 kinase complex, and prevents its recruitment to transcription sites. These results indicate that Pgc is a cell-type-specific P-TEFb inhibitor that has a fundamental role in Drosophila germ cell specification. In C. elegans embryos, PIE-1 protein segregates to germline blastomeres, and is thought to repress mRNA transcription through interaction with P-TEFb4,5,6,7. Thus, inhibition of P-TEFb is probably a common mechanism during germ cell specification in the disparate organisms C. elegans and Drosophila.
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We thank K. Zinn for the lambda phage genomic clone containing the gp150 region, P. Rørth and E. R. Gavis for plasmids, J. T. Lis, D. H. Price and S. Larochelle for antibodies, the Berkeley Drosophila Genome Project and the Bloomington Drosophila stock center for fly stocks, and J. Nakayama, M. Ukai-Tadenuma and H. R. Ueda for technical advice on ChIP analysis. This work was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, and Japan Society of the Promotion of Science, Japan and the RIKEN President Discretionary Fund (to A.N.), and by grants from CIHR and NICHD (to P.L.).
Author Contributions K.H.-N., P. L. and A.N. conceived and designed the experiments. K.H.-N., H.S.-N., A T. and A. N. performed the experiments and generated all the figures. P.L. and A.N. wrote the paper.
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Hanyu-Nakamura, K., Sonobe-Nojima, H., Tanigawa, A. et al. Drosophila Pgc protein inhibits P-TEFb recruitment to chromatin in primordial germ cells. Nature 451, 730–733 (2008). https://doi.org/10.1038/nature06498
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