Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain.
Ten-eleven translocation 1 mediated-DNA hydroxymethylation is required for myelination and remyelination in the mouse brain.
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小鼠大脑中髓鞘形成和髓鞘再生需要 10-11 易位 1 介导的 DNA 羟甲基化
DOI：
10.1038/s41467-021-25353-5
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发表时间：
2021-08-24
影响因子：
16.6
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Zhang M;Wang J;Zhang K;Lu G;Liu Y;Ren K;Wang W;Xin D;Xu L;Mao H;Xing J;Gao X;Jin W;Berry K;Mikoshiba K;Wu S;Lu QR;Zhao X
10 - 11易位（泰特）蛋白是DNA羟甲基化的双加氧酶，在神经系统发育和疾病中起重要作用。然而，它们在损伤后髓鞘形成和髓鞘再生中的作用仍然是难以捉摸的。在这里，我们确定了一个全基因组和基因座特异性DNA羟甲基化景观转移少突胶质细胞祖细胞（OPC）的分化过程中。Tet 1的消融导致小鼠脑中少突胶质细胞（OL）发育和髓鞘形成的阶段依赖性缺陷。在少突胶质细胞谱系中缺乏Tet 1的小鼠发展为行为缺陷。我们还表明，TET 1是需要在成年期髓鞘再生。转录组学、基因组学和5-羟甲基胞嘧啶（5-hydroxymethylcytosine，5 hmC）分析揭示了TET 1调控的少突胶质细胞分化的表观遗传学过程，包括与髓鞘形成、细胞分裂和钙转运相关的基因。TET 1 - 5 hmC靶基因Itpr 2的缺失损害OPC分化的开始。总之，我们的研究结果表明，阶段特异性TET 1介导的表观遗传编程和细胞内信号传导对小鼠的适当髓鞘形成和髓鞘再生很重要。
Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation ofTet1results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lackingTet1in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport.Tet1-deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene,Itpr2, impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice.
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影响因子：
4.5
作者：
Hornig J;Fröb F;Vogl MR;Hermans-Borgmeyer I;Tamm ER;Wegner M
通讯作者：
Wegner M
影响因子：
11
作者：
Harripaul, R.;Vasli, N.;Vincent, J. B.
通讯作者：
Vincent, J. B.
G1/S 相变期间 Rb 磷酸化需要 Tet1
DOI：
10.1016/j.bbrc.2013.02.110
发表时间：
2013-05-03
影响因子：
3.1
作者：
Huang, Shengsong;Zhu, Ziqi;Wu, Denglong
通讯作者：
Wu, Denglong
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：
16
作者：
Brahma, Sandipan;Henikoff, Steven
通讯作者：
Henikoff, Steven