Glycolytic metabolism influences global chromatin structure

Oncotarget
Xue-Song LiuZhi-Min Yuan

Abstract

Metabolic rewiring, specifically elevated glycolytic metabolism is a hallmark of cancer. Global chromatin structure regulates gene expression, DNA repair, and also affects cancer progression. But the interrelationship between tumor metabolism and chromatin architecture remain unclear. Here we show that increased glycolysis in cancer cells promotes an open chromatin configuration. Using complementary methods including Micrococcal nuclease (MNase) digestion assay, electron microscope and immunofluorescence staining, we demonstrate that glycolysis inhibition by pharmacological and genetic approaches was associated with induction of compacted chromatin structure. This condensed chromatin status appeared to result chiefly from histone hypoacetylation as restoration of histone acetylation with an HDAC inhibitor reversed the compacted chromatin state. Interestingly, glycolysis inhibition-induced chromatin condensation impeded DNA repair efficiency leading to increased sensitivity of cancer cells to DNA damage drugs, which may represent a novel molecular mechanism that can be exploited for cancer therapy.

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Citations

Jun 4, 2016·Molecular Medicine·Zhiqiang ZhaoLijun Di
Oct 26, 2018·Frontiers in Genetics·Vera Miranda-GonçalvesCarmen Jerónimo
Sep 25, 2015·Cancer & Metabolism·Ahmad A CluntunJason W Locasale
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Feb 7, 2021·Developmental Biology·Debadrita BhattacharyaMarcos Simoes-Costa
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale
May 15, 2021·Frontiers in Cell and Developmental Biology·Rui MaXilan Yu

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Methods Mentioned

BETA
acetylation
electrophoresis
transmission electron microscopy
sumoylation
histone acetylation
confocal microscopy
Assay

Software Mentioned

CometScoreTM

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