@article{056389588fe24b1eaf94245c24538273,
title = "H2A monoubiquitination links glucose availability to epigenetic regulation of the endoplasmic reticulum stress response and cancer cell death",
abstract = "Epigenetic regulation of gene transcription has been shown to coordinate with nutrient availability, yet the mechanisms underlying this coordination remain incompletely understood. Here, we show that glucose starvation suppresses histone 2A K119 monoubiquitination (H2Aub), a histone modification that correlates with gene repression. Glucose starvation suppressed H2Aub levels independently of energy stress–mediated AMP-activated protein kinase activation and possibly through NADPH depletion and subsequent inhibition of BMI1, an integral component of polycomb-repressive complex 1 (PRC1) that catalyzes H2Aub on chromatin. Integrated transcriptomic and epigenomic analyses linked glucose starvation–mediated H2Aub repression to the activation of genes involved in the endoplasmic reticulum (ER) stress response. We further showed that this epigenetic mechanism has a role in glucose starvation–induced cell death and that pharmacologic inhibition of glucose transporter 1 and PRC1 synergistically promoted ER stress and suppressed tumor growth in vivo. Together, these results reveal a hitherto unrecognized epigenetic mechanism coupling glucose availability to the ER stress response.",
author = "Yilei Zhang and Jiejun Shi and Xiaoguang Liu and Zhenna Xiao and Guang Lei and Hyemin Lee and Pranavi Koppula and Weijie Cheng and Chao Mao and Li Zhuang and Li Ma and Wei Li and Boyi Gan",
note = "Funding Information: We thank the members of the Gan laboratory for their advice and technical assistance. We thank Christine F. Wogan at the Department of Radiation Oncology of MD Anderson Cancer Center for article editing. This research was supported by Bridge Funding from The University of Texas MD Anderson Cancer Center, a next generation sequencing allowance from the Center for Cancer Epigenetics at MD Anderson Cancer Center, a Career Enhancement Award from UT SPORE in Lung Cancer NIH/NCI 5P50CA070907, grant KC180131 from Department of Defense Kidney Cancer Research Program, grant R01CA181196 from the NIH (to B. Gan), grants R01HG007538, R01CA193466, and R01CA228140 from the NIH (to W. Li), and by the Cancer Center Support (Core) Grant P30CA016672 from the NCI, NIH. Y. Zhang and P. Koppula were Scholars at the Center for Cancer Epigenetics at MD Anderson. P. Koppula is also supported by Cancer Prevention and Research Institute of Texas (CPRIT) Research Training Grant RP170067 and by the Dr. John J. Kopchick Research Award from the MD Anderson UTHealth Graduate School of Biomedical Sciences. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = jun,
doi = "10.1158/0008-5472.CAN-19-3580",
language = "English (US)",
volume = "80",
pages = "2243--2256",
journal = "Cancer Research",
issn = "0008-5472",
number = "11",
}