Reprogramming human fibroblasts to neurons by recapitulating an essential microRNA-chromatin switch.

Reprogramming human fibroblasts to neurons by recapitulating an essential microRNA-chromatin switch.
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DOI:
10.1016/j.gde.2013.07.001
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发表时间:
2013-10
影响因子:
4
通讯作者:
Crabtree, Gerald R.
Crabtree, Gerald R.
中科院分区:
生物学2区
文献类型:
--
作者:
Tang, Jiong;Yoo, Andrew S.;Crabtree, Gerald R.

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脊椎动物神经系统的发育需要ATP依赖的染色质重塑机制的转换,其通过在细胞周期出口附近替换这些复合物内的亚基而发生。这种转换涉及三重阴性遗传回路,其中REST抑制miR-9和miR-124,其继而抑制BAF 53 a,其继而抑制同源神经元特异性BAF 53 b。人类成纤维细胞中这种microRNA/染色质开关的重演将它们转化为神经元。参与这种决定命运的染色质转换的基因在几种人类神经系统疾病中起遗传主导作用,这表明它们对人类神经发育的各个方面具有限速作用。我们回顾这种开关在ATP依赖的染色质复合物可能与传统的想法,神经决定和重编程接口。
The development of the vertebrate nervous system requires a switch of ATP-dependent chromatin remodeling mechanisms, which occures by substituting subunits within these complexes near cell cycle exit. This switching involves a triple negative genetic circuitry in which REST represses miR-9 and miR-124, which in turn repress BAF53a, which in turn repress the homologous neuron-specific BAF53b. Recapitulation of this microRNA/chromatin switch in human fibroblasts converts them to neurons. The genes involved in this fate-determining chromatin switch play genetically dominant roles in several human neurologic diseases suggesting that they are rate-limiting for aspects of human neural development. We review how this switch in ATP-dependent chromatin complexes might interface with traditional ideas about neural determination and reprogramming.
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