H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis

被引：37

作者：

Zhang, Xian ^{[1
,2
,3
]}

Li, Binkui ^{[2
]}

Rezaeian, Abdol Hossein ^{[2
]}

Xu, Xiaohong ^{[2
]}

Chou, Ping-Chieh ^{[1
,2
]}

Jin, Guoxiang ^{[1
,2
]}

Han, Fei ^{[1
,2
,3
]}

Pan, Bo-Syong ^{[1
,2
]}

Wang, Chi-Yun ^{[1
,2
]}

Long, Jie ^{[1
,2
]}

Zhang, Anmei ^{[1
,2
]}

Huang, Chih-Yang ^{[4
,5
]}

Tsai, Fuu-Jen ^{[6
,7
]}

Tsai, Chang-Hai ^{[5
,8
]}

Logothetis, Christopher ^{[9
]}

Lin, Hui-Kuan ^{[1
,2
,3
,4
,5
]}

机构：

[1] Wake Forest Sch Med, Dept Canc Biol, Med Ctr Blvd, Winston Salem, NC 27157 USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[3] Univ Texas Grad Sch Biomed Sci Houston, Houston, TX 77030 USA

[4] China Med Univ, Grad Inst Basic Med Sci, Taichung 404, Taiwan

[5] Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan

[6] China Med Univ, Coll Chinese Med, Taichung 40402, Taiwan

[7] China Med Univ Hosp, Dept Med Genet Pediat & Med Res, Taichung 40402, Taiwan

[8] China Med Univ Hosp, Ctr Mol Med, Taichung 40402, Taiwan

[9] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

CANCER STEM-CELLS; HISTONE ACETYLATION; LIGASE NEDD4-1; CHROMATIN; GENOME; PHOSPHORYLATION; METABOLISM; ACTIVATION; PATTERNS; PLATFORM;

D O I：

10.1038/ncomms14799

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular importance. Here we show that, in a glucose-dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on lysine 23/36/37 residues, which specifically recruits histone acetyltransferase GCN5 for subsequent H3 acetylation. Genome-wide analysis of chromatin immunoprecipitation followed by sequencing reveals that NEDD4 regulates glucose-induced H3 K9 acetylation at transcription starting site and enhancer regions. Integrative analysis of ChIP-seq and microarray data sets also reveals a consistent role of NEDD4 in transcription activation and H3 K9 acetylation in response to glucose. Functionally, we show that NEDD4-mediated H3 ubiquitination, by transcriptionally activating IL1 alpha, IL1 beta and GCLM, is important for tumour sphere formation. Together, our study reveals the mechanism for glucose-induced transcriptome reprograming and epigenetic regulation in cancer by inducing NEDD4-dependent H3 ubiquitination.

引用

页数：15

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