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H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis

Publication ,  Journal Article
Zhang, X; Li, B; Rezaeian, AH; Xu, X; Chou, P-C; Jin, G; Han, F; Pan, B-S; Wang, C-Y; Long, J; Zhang, A; Huang, C-Y; Tsai, F-J; Tsai, C-H ...
Published in: Nature Communications
March 16, 2017
Published version (DOI) Publisher Link

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 IL1α, IL1β 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.

Duke Scholars

Hui-Kuan Lin
Author Hui-Kuan Lin Pathology
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Published In

Nature Communications

DOI

10.1038/ncomms14799

EISSN

2041-1723

Publication Date

March 16, 2017

Volume

8

Issue

1

Publisher

Springer Science and Business Media LLC
 

Citation

APA
Chicago
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Zhang, X., Li, B., Rezaeian, A. H., Xu, X., Chou, P.-C., Jin, G., … Lin, H.-K. (2017). H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nature Communications, 8(1). https://doi.org/10.1038/ncomms14799
Zhang, Xian, Binkui Li, Abdol Hossein Rezaeian, Xiaohong Xu, Ping-Chieh Chou, Guoxiang Jin, Fei Han, et al. “H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis.” Nature Communications 8, no. 1 (March 16, 2017). https://doi.org/10.1038/ncomms14799.
Zhang X, Li B, Rezaeian AH, Xu X, Chou P-C, Jin G, et al. H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nature Communications. 2017 Mar 16;8(1).
Zhang, Xian, et al. “H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis.” Nature Communications, vol. 8, no. 1, Springer Science and Business Media LLC, Mar. 2017. Crossref, doi:10.1038/ncomms14799.
Zhang X, Li B, Rezaeian AH, Xu X, Chou P-C, Jin G, Han F, Pan B-S, Wang C-Y, Long J, Zhang A, Huang C-Y, Tsai F-J, Tsai C-H, Logothetis C, Lin H-K. H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nature Communications. Springer Science and Business Media LLC; 2017 Mar 16;8(1).

Published In

Nature Communications

DOI

10.1038/ncomms14799

EISSN

2041-1723

Publication Date

March 16, 2017

Volume

8

Issue

1

Publisher

Springer Science and Business Media LLC