E-GEOD-51512 - Gene expression profiling of BIX01294-treated human neuroblastoma cell line BE(2)-C
Released on 23 October 2013, last updated on 28 October 2013
Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. G9A inactivation depletes serine and its downstream metabolites, triggering cell death with autophagy in cancer cell lines of different tissue origins. Higher G9A expression, which is observed in various cancers and is associated with greater mortality in cancer patients, increases serine production and enhances the proliferation and tumorigenicity of cancer cells. These findings identify a G9A-dependent epigenetic program in the control of cancer metabolism, providing a rationale for G9A inhibition as a therapeutic strategy for cancer. Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C cells treated either with 0.05% DMSO or with 5 µM BIX01294 (B9311, Sigma-Aldrich) for 24 hours.
transcription profiling by array
Justin Choi <firstname.lastname@example.org>, Han-Fei Ding, Jane Ding