Fine-Tuning Mybl2 Is Required for Proper Mesenchymal-to-Epithelial Transition during Somatic Reprogramming.
Fine-Tuning Mybl2 Is Required for Proper Mesenchymal-to-Epithelial Transition during Somatic Reprogramming.
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DOI：
10.1016/j.celrep.2018.07.026
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发表时间：
2018-08-07
期刊：
影响因子：
8.8
通讯作者：
García P
中科院分区：
文献类型：
--
作者：
Ward C;Volpe G;Cauchy P;Ptasinska A;Almaghrabi R;Blakemore D;Nafria M;Kestner D;Frampton J;Murphy G;Buganim Y;Kaji K;García P
在体细胞重编程期间，山中的先锋因子调节一系列复杂的分子事件，导致多能性因子网络的激活，最终导致获得和维持多能性状态。在这里，我们表明，与迄今研究的多能性因素相反，Mybl2的过表达抑制了体细胞重新编程。我们的结果表明，Mybl2基因水平对重新编程过程的动态至关重要。Mybl2的过表达改变了染色质的构象，影响了先驱因子对染色质的可及性，并促进了已知为重编程阻滞剂的早期即时反应基因的可及性。染色质格局的这些变化最终导致对间充质向上皮细胞转变至关重要的关键基因的放松调控。这项工作将Mybl2水平定义为启动重新编程的守门人，为重新编程过程中细胞命运身份的变化所必需的分子事件的严格调控和所需的协调提供了进一步的见解。MYBL2多能性因子的缺失和过表达抑制体细胞重编程Mybl2过表达影响先驱因子对染色质的可及性Mybl2过表达促进重编程阻滞剂对染色质的可及性高Mybl2水平解除对适当MET的关键基因调控，这是重新编程Ward等人的要求。表明Mybl2的表达水平是启动重新编程的守门人。他们发现Mybl2的过度表达导致染色质景观的变化，影响先驱因子对染色质的可及性，并促进AP1转录因子家族的可及性，已知AP1家族是重新编程的阻滞剂。
During somatic reprogramming, Yamanaka’s pioneer factors regulate a complex sequence of molecular events leading to the activation of a network of pluripotency factors, ultimately resulting in the acquisition and maintenance of a pluripotent state. Here, we show that, contrary to the pluripotency factors studied so far, overexpression of Mybl2 inhibits somatic reprogramming. Our results demonstrate that Mybl2 levels are crucial to the dynamics of the reprogramming process. Mybl2 overexpression changes chromatin conformation, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for early immediate response genes known to be reprogramming blockers. These changes in the chromatin landscape ultimately lead to a deregulation of key genes that are important for the mesenchymal-to-epithelial transition. This work defines Mybl2 level as a gatekeeper for the initiation of reprogramming, providing further insights into the tight regulation and required coordination of molecular events that are necessary for changes in cell fate identity during the reprogramming process. Deletion and overexpression of MYBL2 pluripotency factor inhibit somatic reprogramming Mybl2 overexpression affects the accessibility of pioneer factors to the chromatin Mybl2 overexpression promotes accessibility of reprogramming blockers to the chromatin High Mybl2 levels deregulate key genes for proper MET, a requirement for reprogramming Ward et al. show that Mybl2 expression level is a gatekeeper for the initiation of reprogramming. They find that Mybl2 overexpression leads to changes in the chromatin landscape, affecting the accessibility of pioneer factors to the chromatin and promoting accessibility for the AP1 family of transcription factors, known to be reprogramming blockers.
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影响因子：
4
作者：
García, P;Frampton, J
通讯作者：
Frampton, J
DOI：
10.4049/jimmunol.1602033
发表时间：
2017-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Brignall R;Cauchy P;Bevington SL;Gorman B;Pisco AO;Bagnall J;Boddington C;Rowe W;England H;Rich K;Schmidt L;Dyer NP;Travis MA;Ott S;Jackson DA;Cockerill PN;Paszek P
通讯作者：
Paszek P
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
5.2
作者：
Lorvellec, Maelle;Dumon, Stephanie;Maya-Mendoza, Apolinar;Jackson, Dean;Frampton, Jon;Garcia, Paloma
通讯作者：
Garcia, Paloma
影响因子：
4
作者：
Hoppler, Stefan;Kavanagh, Claire Louise
通讯作者：
Kavanagh, Claire Louise