The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells

被引:2
作者
An, Mingrui [1 ,2 ]
Shen, Hongyan [3 ]
Cao, Jun [4 ]
Pei, Xiucong [5 ]
Chang, Yanxu [6 ]
Ma, Shuaipeng [7 ]
Bao, Jintao [7 ]
Zhang, Xuefei [7 ]
Bai, Xue [7 ]
Ma, Yuanhui [7 ]
机构
[1] Cedars Sinai Med Ctr, Dept Surg & Biomed Sci, Los Angeles, CA 90048 USA
[2] Univ Michigan, Dept Surg, Med Ctr, Ann Arbor, MI 48109 USA
[3] Chinese Acad Sci, Beijing Inst Genom, China Gastrointestinal Canc Res Ctr, Key Lab Genom & Precis Med, Beijing 100101, Peoples R China
[4] Hangzhou Normal Univ, Coll Mat Chem & Chem Engn, Hangzhou 310036, Zhejiang, Peoples R China
[5] Shenyang Med Coll, Sch Publ Hlth, Dept Toxicol, Shenyang 110034, Liaoning, Peoples R China
[6] Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, Tianjin 300193, Peoples R China
[7] Peking Univ, Coll Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
关键词
Differentiation; Histone modifications; NSCs; SILAC; MASS-SPECTROMETRY; POSTTRANSLATIONAL MODIFICATIONS; METHYLTRANSFERASE ACTIVITY; CHARGE DERIVATIZATION; RETINOIC ACID; EXPRESSION; DROSOPHILA; CHROMATIN; HISTONES; H3;
D O I
10.1016/j.ab.2016.07.005
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique. Then we induced these NSCs to differentiate by all-trans retinoic acid (atRA) or SB216763. Next, we identified the alteration of histone modifications in early-differentiated NSCs by mass spectrometry and verified them by Western blot. Interestingly, these modification alterations and phenotype changes were found similar in NSCs induced by the two different drugs. More interestingly, during the differentiation process H3-K27met was significantly up-regulated while H4Kl6ac was not altered at the global level but down-regulated in some low-abundance combinatorial codes. We inhibited the methyltransferase of H3-K27 and deacetylase of H4-K16 simultaneously and found the differentiation procedure was obviously delayed. The function of H4-K16ac and H3-K27met in NSCs differentiation would be useful to reveal the differentiation mechanism and valuable for further neural stem cell therapy. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:92 / 99
页数:8
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