GlcNAcylation of histone H2B facilitates its monoubiquitination.
GlcNAcylation of histone H2B facilitates its monoubiquitination.
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DOI：
10.1038/nature10656
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发表时间：
2011-11-27
期刊：
影响因子：
64.8
通讯作者：
Kato S
中科院分区：
文献类型：
--
作者：
Fujiki R;Hashiba W;Sekine H;Yokoyama A;Chikanishi T;Ito S;Imai Y;Kim J;He HH;Igarashi K;Kanno J;Ohtake F;Kitagawa H;Roeder RG;Brown M;Kato S
组蛋白尾部的翻译后修饰产生定义局部和全局染色质状态的“组蛋白密码”。由此产生的基因功能调节被认为支配细胞命运、增殖和分化。可逆的组蛋白修饰，如甲基化是在相互控制下组织染色体事件。在组蛋白修饰中，特定赖氨酸和精氨酸残基的甲基化似乎对染色质构型和基因表达的控制至关重要。组蛋白H3赖氨酸4（H3 K4）的甲基化将染色质改变成转录活性状态。β-N-乙酰葡糖胺（O-GlcNAc）对蛋白质的可逆修饰可响应血清葡萄糖水平，调节多种细胞过程。然而，蛋白GlcNAc化的表观遗传影响是未知的。在这里，我们报告，核GlcNAc修饰的组蛋白赖氨酸甲基转移酶（HKMT），MLL 5，通过O-GlcNAc转移酶促进维甲酸诱导的粒细胞生成在人类HL 60早幼粒细胞通过甲基化H3 K4。MLL 5在与核视黄酸受体RARα（也称为RARA）相关的GlcNAcylation依赖性多亚基复合物中被生化鉴定，作为H3 K4的单甲基和二甲基转移酶。MLL 5 SET结构域中Thr 440处的GlcNAc化引起其H3 K4 HKMT活性并共激活靶基因启动子中的RARα。通过O-GlcNAc转移酶增加核GlcNAc酰化增强视黄酸诱导的HL 60粒细胞生成并恢复视黄酸抗性HL 60-R2细胞系中的视黄酸反应因此，核MLL 5 GlcNAc化通过激活其HKMT活性触发HL 60的细胞谱系确定。
The post-translational modifications of histone tails generate a ‘histone code’ that defines local and global chromatin states. The resultant regulation of gene function is thought to govern cell fate, proliferation and differentiation. Reversible histone modifications such as methylation are under mutual controls to organize chromosomal events. Among the histone modifications, methylation of specific lysine and arginine residues seems to be critical for chromatin configuration and control of gene expression. Methylation of histone H3 lysine 4 (H3K4) changes chromatin into a transcriptionally active state. Reversible modification of proteins by β-N-acetylglucosamine (O-GlcNAc) in response to serum glucose levels regulates diverse cellular processes. However, the epigenetic impact of protein GlcNAcylation is unknown. Here we report that nuclear GlcNAcylation of a histone lysine methyltransferase (HKMT), MLL5, by O-GlcNAc transferase facilitates retinoic-acid-induced granulopoiesis in human HL60 promyelocytes through methylation of H3K4. MLL5 is biochemically identified in a GlcNAcylation-dependent multi-subunit complex associating with nuclear retinoic acid receptor RARα (also known as RARA), serving as a mono- and di-methyl transferase to H3K4. GlcNAcylation at Thr440 in the MLL5 SET domain evokes its H3K4 HKMT activity and co-activates RARα in target gene promoters. Increased nuclear GlcNAcylation by means of O-GlcNAc transferase potentiates retinoic-acid-induced HL60 granulopoiesis and restores the retinoic acid response in the retinoic-acid-resistant HL60-R2 cell line. Thus, nuclear MLL5 GlcNAcylation triggers cell lineage determination of HL60 through activation of its HKMT activity.
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影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
影响因子：
64.8
作者：
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通讯作者：
Kato, Shigeaki
影响因子：
7.3
作者：
Wang Z;Udeshi ND;Slawson C;Compton PD;Sakabe K;Cheung WD;Shabanowitz J;Hunt DF;Hart GW
通讯作者：
Hart GW
影响因子：
64.8
作者：
Das, Chandrima;Lucia, M. Scott;Hansen, Kirk C.;Tyler, Jessica K.
通讯作者：
Tyler, Jessica K.
影响因子：
56.9
作者：
Gambetta, Maria Cristina;Oktaba, Katarzyna;Mueller, Juerg
通讯作者：
Mueller, Juerg