Epigenetic drift towards histone modifications regulates CAV1 gene expression in colon cancer

• CAV1 is an important structural and signaling protein in the membrane caveolae.
• Promoter DNA methylation does not play any important role in CAV1 regulation.
• CAV1 expression is regulated by enrichment of H3K4me3 and H3K9AcS10P, and depletion of H3K9me3.
• Ectopic expression of CAV1 increases apoptosis and decreases aggressiveness in colon cancer.

BackgroundCaveolin-1 (CAV1) is an important structural component of cellular caveolae involved in cell signaling. CAV1 gene on/off regulatory mechanism in multiple diseases, including cancer is not clearly understood. The tumor suppressor versus oncogene paradox of CAV1 during tumor development tempted us to investigate the role for the epigenetic drift of CAV1 gene regulation.MethodsWe have analyzed CAV1 gene expression and associated epigenetic marks (DNA methylation and histone 3 modifications) in the CAV1 promoter in two colon cancer cell lines, under treatment with well established epigenetic modulators, AZA, SAM, TSA and SFN at varying concentrations. CAV1 gene promoter DNA methylation and histone modifications were analyzed by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR respectively.ResultsEctopic expression of CAV1 by epigenetic modulators inhibits colon cancer cell growth. CAV1 promoter DNA remains unmethylated before and after treatment with epigenetic modulators, which confirmed that DNA methylation is not the regulator of CAV1 expression in colon cancer. There was enrichment of H3K4me3 and H3K9AcS10P and depletion of H3K9me3 modifications around the CAV1 promoter.ConclusionsOur data provides novel insight into the regulation of CAV1 gene by histone H3 modifications and enhance the amplitude of the cancer epigenome.