A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.
A C. elegans LSD1 demethylase contributes to germline immortality by reprogramming epigenetic memory.
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DOI：
10.1016/j.cell.2009.02.015
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发表时间：
2009-04-17
期刊：
影响因子：
64.5
通讯作者：
Kelly WG
中科院分区：
文献类型：
--
作者：
Katz DJ;Edwards TM;Reinke V;Kelly WG
最近，已经提出组蛋白H3在赖氨酸4上的二甲基化（H3 K4 me 2）作为表观遗传记忆来维持发育组织中的转录模式。这个模型表明，可能需要在生殖细胞中重新编程这种修饰，以防止转录记忆被不适当地传递给下一代。我们问SPR-5，C。H3 K4 me 2脱甲基酶LSD 1/KDM 1的直向同源物，在表观遗传学重编程H3 K4 me 2中起作用。我们发现，由于卵子发生和精子发生的缺陷，spr-5突变体在多代中表现出进行性不育。这些缺陷与在原始生殖细胞中清除H3 K4 me 2的进行性失败相关，由于H3 K4 me 2在这些位点的跨代积累，导致精子发生表达基因的失调。这些结果表明，H3 K4 me 2可以作为一种表观遗传记忆，LSD 1/KDM 1去甲基化酶在生殖系中对这种记忆的重编程中发挥关键作用，防止不适当的表观遗传信息从一代传播到下一代。
Recently it has been proposed that di-methylation of histone H3 on lysine 4 (H3K4me2) acts as an epigenetic memory to maintain transcriptional patterns in developing tissues. This model suggests that there may be a requirement to reprogram this modification in the germline to prevent transcriptional memory from being inappropriately transmitted to the next generation. We asked if SPR-5, the C. elegans ortholog of the H3K4me2 demethylase LSD1/KDM1, plays a role in epigenetically reprogramming H3K4me2. We show that spr-5 mutants exhibit progressive sterility over many generations due to defects in oogenesis and spermatogenesis. These defects correlate with a progressive failure to erase H3K4me2 in the primordial germ cells, resulting in the misregulation of spermatogenesis-expressed genes due to the transgenerational accumulation of H3K4me2 at these loci. These results suggest that H3K4me2 can serve as an epigenetic memory and that LSD1/KDM1 demethylases play a critical role in the reprogramming of this memory in the germline, preventing inappropriate epigenetic information from being propagated from one generation to the next.
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