Department of Zoology, University of Fribourg, Chemin du musée 10, 1700 Fribourg, Switzerland.
Stem Cell Reports. 2014 Mar 27;2(4):547-59. doi: 10.1016/j.stemcr.2014.02.007. eCollection 2014 Apr 8.
Throughout their journey to forming new individuals, germline stem cells must remain totipotent, particularly by maintaining a specific chromatin structure. However, the place epigenetic factors occupy in this process remains elusive. So far, "sensitization" of chromatin by modulation of histone arrangement and/or content was believed to facilitate transcription-factor-induced germ cell reprogramming. Here, we demonstrate that the combined reduction of two epigenetic factors suffices to reprogram C. elegans germ cells. The histone H3K4 demethylase SPR-5/LSD1 and the chromatin remodeler LET-418/Mi2 function together in an early process to maintain germ cell status and act as a barrier to block precocious differentiation. This epigenetic barrier is capable of limiting COMPASS-mediated H3K4 methylation, because elevated H3K4me3 levels correlate with germ cell reprogramming in spr-5; let-418 mutants. Interestingly, germ cells deficient for spr-5 and let-418 mainly reprogram as neurons, suggesting that neuronal fate might be the first to be derepressed in early embryogenesis.
在形成新个体的过程中，生殖干细胞必须保持全能性，尤其是通过维持特定的染色质结构。然而，表观遗传因素在这个过程中所占据的位置仍然难以捉摸。到目前为止，通过调节组蛋白排列和/或含量来“敏化”染色质被认为可以促进转录因子诱导的生殖细胞重编程。在这里，我们证明了两种表观遗传因素的联合减少足以重编程秀丽隐杆线虫的生殖细胞。组蛋白 H3K4 去甲基酶 SPR-5/LSD1 和染色质重塑因子 LET-418/Mi2 共同作用于一个早期过程，以维持生殖细胞状态，并作为阻止过早分化的障碍。这种表观遗传障碍能够限制 COMPASS 介导的 H3K4 甲基化，因为在 spr-5; let-418 突变体中，升高的 H3K4me3 水平与生殖细胞重编程相关。有趣的是，spr-5 和 let-418 缺失的生殖细胞主要重编程为神经元，这表明在早期胚胎发生中，神经元命运可能是第一个被去抑制的。
