SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line
SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state during passage through the germ line
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DOI：
10.1073/pnas.1321843111
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发表时间：
2014-07-01
影响因子：
11.1
通讯作者：
Katz, David J.
中科院分区：
文献类型：
--
作者：
Kerr, Shana C.;Ruppersburg, Chelsey Chandler;Katz, David J.
秀丽隐杆线虫LSD 1 H3 K4 me 2去甲基化酶SPR-5在通过生殖系期间重编程表观遗传转录记忆。在这里，我们表明，突变体中的H3 K9 me 2甲基转移酶，Met-2，导致跨代表观遗传效应，平行的SPR-5突变体。此外，我们发现spr-5; met-2双突变体对不育、H3 K4 me 2和精子发生表达具有协同作用。这些结果暗示MET-2作为生殖系重编程中的第二组蛋白修饰酶，并提出SPR-5和MET-2协同作用以重建C.线虫生殖系在没有SPR-5和MET-2的情况下，我们发现表达精子发生基因的能力被转代传递给下一代的体细胞。这表明H3 K4 me 2可能在维持细胞命运中起作用。最后，我们证明了减少H3 K4 me 2导致由SPR-5; MET-2重编程机制添加的H3 K9 me 2大量增加。这一发现表明了一种新的组蛋白密码子相互作用，其中输入染色质环境决定输出染色质状态。总之，我们的研究结果为更广泛的重编程机制提供了证据，在该机制中，多种酶在通过种系的过程中协调调节组蛋白信息。
The Caenorhabditis elegans LSD1 H3K4me2 demethylase SPR-5 reprograms epigenetic transcriptional memory during passage through the germ line. Here we show that mutants in the H3K9me2 methyltransferase, met-2, result in transgenerational epigenetic effects that parallel spr-5 mutants. In addition, we find that spr-5; met-2 double mutants have a synergistic effect on sterility, H3K4me2, and spermatogenesis expression. These results implicate MET-2 as a second histone-modifying enzyme in germ-line reprogramming and suggest a model in which SPR-5 and MET-2 function cooperatively to reestablish an epigenetic ground state required for the continued immortality of the C. elegans germ line. Without SPR-5 and MET-2, we find that the ability to express spermatogenesis genes is transgenerationally passed on to the somatic cells of the subsequent generation. This indicates that H3K4me2 may act in the maintenance of cell fate. Finally, we demonstrate that reducing H3K4me2 causes a large increase in H3K9me2 added by the SPR-5; MET-2 reprogramming mechanism. This finding suggests a novel histone code interaction in which the input chromatin environment dictates the output chromatin state. Taken together, our results provide evidence for a broader reprogramming mechanism in which multiple enzymes coordinately regulate histone information during passage through the germ line.