Peng Jamy C, Valouev Anton, Liu Na, Lin Haifan
Yale Stem Cell Center, Yale University, New Haven, Connecticut, USA.
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
Nat Genet. 2016 Mar;48(3):283-91. doi: 10.1038/ng.3486. Epub 2016 Jan 18.
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.
果蝇中的Piwi蛋白通过调节微环境和内在机制来维持生殖系干细胞，但具体机制尚不清楚。在此我们报道，Piwi在微环境和生殖细胞中与多梳蛋白组复合物PRC1和PRC2相互作用，以调节卵巢生殖系干细胞和卵子发生。Piwi在卵巢和体外与PRC2亚基Su(z)12和Esc发生物理相互作用。在野生型和piwi突变体卵巢中，对Piwi、PRC2酶亚基E(z)、赖氨酸27三甲基化的组蛋白H3（H3K27me3）和RNA聚合酶II进行染色质共免疫沉淀分析，结果表明Piwi在约72个基因组位点结合一个保守的DNA基序，并抑制PRC2与许多非Piwi结合的基因组靶点结合以及H3K27三甲基化。此外，Piwi可能通过抑制PRC2来影响果蝇卵巢中的RNA聚合酶II活性。我们推测，Piwi通过将PRC2隔离在核质中，负向调节PRC2的结合，从而减少PRC2与许多靶点的结合，并影响卵子发生过程中的转录。
