Transcriptional regulation of ALOX15 promoter in cancer. A, IL‐4 and IL‐13, mediated phosphorylation of STAT‐6 protein allows its entry to the nucleus to act as a transcription factor for 15‐LOX‐ 1. GATA‐6 acts as a repressor of ALOX15 expression; treatment with the HDACi sodium butyrate has been shown to inhibit the binding of GATA‐6 to the promoter, thus enhancing the expression of 15‐LOX‐1. B, Continued acetylation of histones by histone deacetylase inhibitors (HDACi) or acetylation of histones with histone acetyl transferases (HATs) such as CBP/p300 prevents chromatin condensation and induce the expression of 15‐LOX‐1. C, Methylation of the ALOX15 promoter is a commonly observed in colon cancer samples and cell lines where the gene is silenced. The DNA methyl transferase DNMT‐1 and the chromatin remodelling complex NuRD compete for binding and repress the ALOX15 promoter. HDACi may deactivate the NuRD complex for the re‐expression of 15‐LOX‐1. Treatment with the DNA methyltransferase agent 5‐Aza‐2′‐deoxycytidine(5‐aza‐dC) can de‐methylate the promoter and enhance expression in colon cancer cells.