HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination.
HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination.
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DOI：
10.1038/nn.2780
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发表时间：
2011-04
影响因子：
25
通讯作者：
Lu, Q. Richard
中科院分区：
文献类型：
--
作者：
Chen, Ying;Wang, Haibo;Yoon, Sung Ok;Xu, Xiaomei;Hottiger, Michael O.;Svaren, John;Nave, Klaus A.;Kim, Haesun A.;Olson, Eric N.;Lu, Q. Richard
雪旺氏细胞髓鞘的形成受到及时表达的关键转录调控因子的严格调控，这些转录调控因子对特定的环境信号做出反应，但对这种过程的分子机制知之甚少。在这里，我们报告HDAC 1/2调节的NF-κB的乙酰化状态在编排髓鞘形成程序中是至关重要的。缺乏HDAC 1/2的小鼠表现出严重的髓鞘形成障碍，雪旺细胞发育停滞在未成熟阶段。我们发现NF-κB p65在HDAC 1/2突变体中变得高度乙酰化，抑制髓鞘形成的正调节因子的表达，同时诱导分化抑制因子的表达。我们观察到随着雪旺细胞的分化，NF-κB蛋白复合物将其与p300的结合转变为与HDAC 1/2的结合。NF-κB和HDAC 1/2协同作用，调节雪旺细胞髓鞘形成的转录相关染色质状态。因此，我们的研究结果揭示了HDAC介导的控制周围神经系统髓鞘形成的发育开关。
Schwann cell myelination is tightly regulated by timely expression of key transcriptional regulators that respond to specific environmental cues, yet molecular mechanisms underlying such a process are poorly understood. Here, we report that HDAC1/2-regulated acetylation state of NF-κB is critical in orchestrating the myelination program. Mice lacking HDAC1/2 exhibit severe dysmyelination with Schwann cell development arrested at the immature stage. We find that NF-κB p65 becomes heavily acetylated in HDAC1/2 mutants, inhibiting the expression of positive regulators of myelination, while inducing the expression of differentiation inhibitors. We observe that NF-κB protein complex switches its association with p300 to that with HDAC1/2 as Schwann cells differentiate. NF-κB and HDAC1/2 act coordinately to regulate the transcriptionally-linked chromatin state for Schwann cell myelination. Thus, our results reveal an HDAC-mediated developmental switch for controlling myelination in the peripheral nervous system.
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影响因子：
25
作者：
Chen, Ying;Wu, Heng;Wang, Shuzong;Koito, Hisami;Li, Jianrong;Ye, Feng;Hoang, Jenny;Escobar, Sabine S.;Gow, Alexander;Arnett, Heather A.;Trapp, Bruce D.;Karandikar, Nitin J.;Hsieh, Jenny;Lu, Q. Richard
通讯作者：
Lu, Q. Richard
影响因子：
25
作者：
Nickols, JC;Valentine, W;Carter, BD
通讯作者：
Carter, BD
影响因子：
25
作者：
Shen, Siming;Sandoval, Juan;Swiss, Victoria A.;Li, Jiadong;Dupree, Jeff;Franklin, Robin J. M.;Casaccia-Bonnefil, Patrizia
通讯作者：
Casaccia-Bonnefil, Patrizia
影响因子：
4.5
作者：
Antonellis, Anthony;Huynh, Jimmy L.;Lee-Lin, Shih-Queen;Vinton, Ryan M.;Renaud, Gabriel;Loftus, Stacie K.;Elliot, Gene;Wolfsberg, Tyra G.;Green, Eric D.;McCallion, Andrew S.;Pavan, William J.
通讯作者：
Pavan, William J.
影响因子：
4.4
作者：
Rothgiesser KM;Fey M;Hottiger MO
通讯作者：
Hottiger MO