Radical acceleration of nuclear reprogramming by chromatin remodeling with the transactivation domain of MyoD.
Radical acceleration of nuclear reprogramming by chromatin remodeling with the transactivation domain of MyoD.
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DOI：
10.1002/stem.684
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发表时间：
2011-09
期刊：
影响因子：
5.2
通讯作者：
Kikyo, Nobuaki
中科院分区：
文献类型：
--
作者：
Hirai, Hiroyuki;Tani, Tetsuya;Katoku-Kikyo, Nobuko;Kellner, Steven;Karian, Peter;Firpo, Meri;Kikyo, Nobuaki
诱导多能干细胞（iPSC）可以通过引入定义的基因（最常见的是Oct 4，Sox 2，Klf 4和c-Myc（OSKM））重新编程分化的细胞来创建。然而，这个过程是缓慢的，而且效率极低。在这里，我们展示了Oct 4和MyoD（M3 O）的强大反式激活结构域（M3 O）之间的融合基因对iPSC创建的根本加速。将M3 O以及Sox 2、Klf 4和c-Myc转导到成纤维细胞中有效地重塑了DNA甲基化、染色质可及性、组蛋白修饰和多能性基因处的蛋白质结合的模式，与OSKM相比，使制造小鼠和人类iPSC的效率提高了50倍以上。这些结果表明，iPSC产生的最关键障碍之一是染色质可及性差和多能性基因的蛋白质募集。MyoD ™具有克服该问题的能力。我们将TADs与不相关的转录因子融合的方法作为转录重编程的强大工具具有深远的意义，超出了iPSC技术的应用。
Induced pluripotent stem cells (iPSCs) can be created by reprogramming differentiated cells through introduction of defined genes, most commonly Oct4, Sox2, Klf4, and c-Myc (OSKM). However, this process is slow and extremely inefficient. Here, we demonstrate radical acceleration of iPSC creation with a fusion gene between Oct4 and the powerful transactivation domain (TAD) of MyoD (M3O). Transduction of M3O as well as Sox2, Klf4, and c-Myc into fibroblasts effectively remodeled patterns of DNA methylation, chromatin accessibility, histone modifications, and protein binding at pluripotency genes, raising the efficiency of making mouse and human iPSCs more than 50-fold in comparison to OSKM. These results identified that one of the most critical barriers to iPSC creation is poor chromatin accessibility and protein recruitment to pluripotency genes. The MyoD TAD has a capability of overcoming this problem. Our approach of fusing TADs to unrelated transcription factors has far-reaching implications as a powerful tool for transcriptional reprogramming beyond application to iPSC technology.
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影响因子：
3.3
作者：
Boxus M;Twizere JC;Legros S;Dewulf JF;Kettmann R;Willems L
通讯作者：
Willems L
影响因子：
9.2
作者：
Horb, ME;Shen, CN;Slack, JMW
通讯作者：
Slack, JMW
影响因子：
64.5
作者：
Niwa, H;Toyooka, T;Rossant, J
通讯作者：
Rossant, J
DOI：
10.1387/ijdb.103194hh
发表时间：
2010
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Hirai H;Tani T;Kikyo N
通讯作者：
Kikyo N
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.