Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia

Xue Gao, Shuhai LIN, Feng Ren, Jin Tao Li, Jia Jia Chen, Chuan Bo Yao, Hong Bin Yang, Shu Xia Jiang, Guo Quan Yan, Di Wang, Yi Wang, Ying Liu, Zongwei CAI, Ying Ying Xu, Jing Chen, Wenqiang Yu, Peng Yuan Yang*, Qun Ying Lei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Citations (Scopus)

Abstract

Besides the conventional carbon sources, acetyl-CoA has recently been shown to be generated from acetate in various types of cancers, where it promotes lipid synthesis and tumour growth. The underlying mechanism, however, remains largely unknown. We find that acetate induces a hyperacetylated state of histone H3 in hypoxic cells. Acetate predominately activates lipogenic genes ACACA and FASN expression by increasing H3K9, H3K27 and H3K56 acetylation levels at their promoter regions, thus enhancing de novo lipid synthesis, which combines with its function as the metabolic precursor for fatty acid synthesis. Acetyl-CoA synthetases (ACSS1, ACSS2) are involved in this acetate-mediated epigenetic regulation. More importantly, human hepatocellular carcinoma with high ACSS1/2 expression exhibit increased histone H3 acetylation and FASN expression. Taken together, this study demonstrates that acetate, in addition to its ability to induce fatty acid synthesis as an immediate metabolic precursor, also functions as an epigenetic metabolite to promote cancer cell survival under hypoxic stress.

Original languageEnglish
Article number11960
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 30 Jun 2016

Scopus Subject Areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint

Dive into the research topics of 'Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia'. Together they form a unique fingerprint.

Cite this