RNF8 mediates histone H3 ubiquitylation and promotes glycolysis and tumorigenesis

The Journal of Experimental Medicine
Yan XiaZhimin Lu

Abstract

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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Citations

Dec 6, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Wladyslaw A Krajewski
Aug 6, 2020·Molecular Cancer Research : MCR·Jingyu KuangLingyun Zhu
Dec 15, 2020·Trends in Biochemical Sciences·Robert M VaughanScott B Rothbart
May 15, 2021·Frontiers in Cell and Developmental Biology·Rui MaXilan Yu
Apr 30, 2021·The FEBS Journal·Merav D ShmueliYifat Merbl
Mar 24, 2021·Molecular and Cellular Biology·Ann K Hogan, Daniel R Foltz

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Methods Mentioned

BETA
acetylation
immunoprecipitation
pull-down
coimmunoprecipitation
PCR
electron microscopy
ChIP
PCRs
xenografts
transfection

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