Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins.
Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins.
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DOI：
10.1038/ng.3486
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发表时间：
2016-03
期刊：
影响因子：
30.8
通讯作者：
Lin H
中科院分区：
文献类型：
--
作者：
Peng JC;Valouev A;Liu N;Lin H
果蝇Piwi蛋白调节生态位和内在机制以维持生殖系干细胞，但其潜在机制仍不清楚。在这里，我们报告Piwi与Polycomb Group复合物PRC 1和PRC 2在生态位和生殖系细胞中合作，以调节卵巢生殖系干细胞和卵子发生。Piwi在卵巢和体外与PRC 2亚基Su（z）12和ESC物理相互作用。Piwi、PRC 2酶亚基E（z）、赖氨酸-27-三甲基化组蛋白3（H3 K27 m3）和RNA聚合酶II在野生型和Piwi突变卵巢中的染色质免疫共沉淀揭示，Piwi在约72个基因组位点处结合保守的DNA基序，并抑制PRC 2与许多非Piwi结合的基因组靶点和H3 K27三甲基化的结合。此外，Piwi可能通过抑制PRC 2影响果蝇卵巢中RNA聚合酶II的活性。我们假设Piwi通过在核质中隔离PRC 2来负调节PRC 2结合，从而减少PRC 2与许多靶点的结合并影响卵子发生过程中的转录。
The Drosophila Piwi protein regulates both niche and intrinsic mechanisms to maintain germline stem cells, but its underlying mechanism remains unclear. Here we report that Piwi cooperates with Polycomb Group complexes PRC1 and PRC2 in niche and germline cells to regulate ovarian germline stem cells and oogenesis. Piwi physically interacts with PRC2 subunits Su(z)12 and Esc in the ovary and in vitro. Chromatin co-immunoprecipitation of Piwi, the PRC2 enzymatic subunit E(z), lysine-27-tri-methylated histone 3 (H3K27m3), and RNA polymerase II in wild-type and piwi mutant ovaries reveals that Piwi binds a conserved DNA motif at ~72 genomic sites, and inhibits PRC2 binding to many non-Piwi-binding genomic targets and H3K27 tri-methylation. 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 influences transcription during oogenesis.