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Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins

Nature Genetics volume 48, pages 283291 (2016) | Download Citation


The Drosophila melanogaster Piwi protein regulates both niche and intrinsic mechanisms to maintain germline stem cells, but its underlying mechanism remains unclear. Here we report that Piwi interacts with Polycomb group complexes PRC1 and PRC2 in niche and germline cells to regulate ovarian germline stem cells and oogenesis. Piwi physically interacts with the PRC2 subunits Su(z)12 and Esc in the ovary and in vitro. Chromatin coimmunoprecipitation of Piwi, the PRC2 enzymatic subunit E(z), histone H3 trimethylated at lysine 27 (H3K27me3) and RNA polymerase II in wild-type and piwi mutant ovaries demonstrates that Piwi binds a conserved DNA motif at 72 genomic sites and inhibits PRC2 binding to many non-Piwi-binding genomic targets and H3K27 trimethylation. Moreover, Piwi influences RNA polymerase II activities in Drosophila ovaries, likely via inhibiting PRC2. We hypothesize that Piwi negatively regulates PRC2 binding by sequestering PRC2 in the nucleoplasm, thus reducing PRC2 binding to many targets and influencing transcription during oogenesis.

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We thank R. Jones (Southern Methodist University) for the E(z)63 fly stock, F. Peronnet (Institut de Biologie, Paris) for the corto420 fly stock, V. Pirotta (Rutgers University) for the antibody to Pc, H. Siomi (Keio University) for the antibody to Piwi, D. Godt (University of Toronto) for the antibody to Tj, and A. Fire and members of the Lin laboratory for assistance and discussions. We also thank H. Qi and J. Klein for experimental help, M. Reddivari for the isolation of recombinant PRC2 complex, Z. Albertyn and C. Hercus for help with Novoalign, and N. Neuenkirchen and X. Cui for critical reading. This work was supported by a US National Institutes of Health Pioneer Award (DP1CA174418) and the Mathers Award to H.L. and by a US National Institutes of Health grant (R00-HD071011) to J.C.P.

Author information

Author notes

    • Jamy C Peng

    Present address: Division of Developmental Biology, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

    • Jamy C Peng
    •  & Anton Valouev

    These authors contributed equally to this work.


  1. Yale Stem Cell Center, Yale University, New Haven, Connecticut, USA.

    • Jamy C Peng
    • , Na Liu
    •  & Haifan Lin
  2. Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Jamy C Peng
    • , Na Liu
    •  & Haifan Lin
  3. Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Anton Valouev
  4. Shanghai Institute of Advanced Immunochemical Studies, Shanghai, China.

    • Haifan Lin
  5. School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

    • Haifan Lin


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J.C.P. and H.L. designed the project, analyzed the data and wrote the manuscript. J.C.P. conducted all of the experiments except for those listed in the Acknowledgments. A.V. produced all bioinformatics results in the paper and participated in manuscript writing. N.L. performed the initial bioinformatics analysis that helped guide the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Jamy C Peng or Haifan Lin.

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