MRG-1/MRG15 Is a Barrier for Germ Cell to Neuron Reprogramming in Caenorhabditis elegans
MRG-1/MRG15 Is a Barrier for Germ Cell to Neuron Reprogramming in Caenorhabditis elegans
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DOI：
10.1534/genetics.118.301674
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发表时间：
2019-01-01
期刊：
影响因子：
3.3
通讯作者：
Tursun, Baris
中科院分区：
文献类型：
--
作者：
Hajduskova, Martina;Baytek, Guelkiz;Tursun, Baris
染色质调节剂通过对抗异位细胞命运的诱导，在保护细胞身份方面发挥重要作用，从而防止通过重编程方法强制转换细胞身份。由于大多数研究都使用组织培养，我们对染色质调节因子在生物体中充当重编程屏障的认识需要改进。我们使用秀丽隐杆线虫作为体内基因发现模型和自动固相 RNA 干扰筛选，通过该筛选，我们确定了 10 种染色质调节因子，可保护细胞免受异位命运诱导。具体来说，染色质结构域蛋白 MRG-1 可保护生殖细胞免于转化为神经元。 MRG-1 是哺乳动物 MRG15（15 号染色体上的 MORF 相关基因）的直系同源物，是秀丽隐杆线虫种系发育过程中所必需的。然而，IVIRG-1 作为生殖细胞重编程屏障的功能此前尚未被揭示。在这里，我们进一步提供了 MRG-1 的蛋白质-蛋白质和基因组相互作用，以表征其分子功能。保守的染色质调节因子在高等生物中可能具有类似的功能，因此，了解线虫中的细胞命运保护也可能有助于促进人类细胞的重编程。
Chromatin regulators play important roles in the safeguarding of cell identities by opposing the induction of ectopic cell fates and, thereby, preventing forced conversion of cell identities by reprogramming approaches. Our knowledge of chromatin regulators acting as reprogramming barriers in living organisms needs improvement as most studies use tissue culture. We used Caenorhabditis elegans as an in vivo gene discovery model and automated solid-phase RNA interference screening, by which we identified 10 chromatin-regulating factors that protect cells against ectopic fate induction. Specifically, the chromodomain protein MRG-1 safeguards germ cells against conversion into neurons. MRG-1 is the ortholog of mammalian MRG15 (MORF-related gene on chromosome 15) and is required during germline development in C. elegans. However, IVIRG-1's function as a barrier for germ cell reprogramming has not been revealed previously. Here, we further provide protein-protein and genome interactions of MRG-1 to characterize its molecular functions. Conserved chromatin regulators may have similar functions in higher organisms, and therefore, understanding cell fate protection in C. elegans may also help to facilitate reprogramming of human cells.