TY - JOUR
T1 - RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis
AU - Xia, Yan
AU - Yang, Weiwei
AU - Fa, Ming
AU - Li, Xinjian
AU - Wang, Yugang
AU - Jiang, Yuhui
AU - Zheng, Yanhua
AU - Lee, Jong Ho
AU - Li, Jing
AU - Lu, Zhimin
N1 - Publisher Copyright:
© 2017 Xia et al.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation and brain tumorigenesis. Our findings uncover the role of RNF8- mediated histone H3 polyubiquitylation in the regulation of histone H3 stability and chromatin modification, paving the way to gene expression regulation and tumorigenesis.
AB - Disassembly of nucleosomes in which genomic DNA is packaged with histone regulates gene expression. However, the mechanisms underlying nucleosome disassembly for gene expression remain elusive. We show here that epidermal growth factor receptor activation results in the binding of the RNF8 forkhead-associated domain to pyruvate kinase M2-phosphorylated histone H3-T11, leading to K48-linked polyubiquitylation of histone H3 at K4 and subsequent proteasome-dependent protein degradation. In addition, H3 polyubiquitylation induces histone dissociation from chromatin, nucleosome disassembly, and binding of RNA polymerase II to MYC and CCND1 promoter regions for transcription. RNF8-mediated histone H3 polyubiquitylation promotes tumor cell glycolysis and proliferation and brain tumorigenesis. Our findings uncover the role of RNF8- mediated histone H3 polyubiquitylation in the regulation of histone H3 stability and chromatin modification, paving the way to gene expression regulation and tumorigenesis.
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U2 - 10.1084/jem.20170015
DO - 10.1084/jem.20170015
M3 - Article
C2 - 28507061
AN - SCOPUS:85021855844
SN - 0022-1007
VL - 214
SP - 1843
EP - 1855
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -