Epigenetic and transcriptional control of the 15-lipoxygenase-1 gene in a Hodgkin lymphoma cell line.
ABSTRACT Lipoxygenases oxidatively metabolize polyunsaturated fatty acids to a rich spectrum of biologically active metabolites. The present study aimed at delineating the transcriptional and epigenetic mechanisms leading to 15-lipoxygenase-1 (15-LOX-1) expression in the Hodgkin lymphoma (HL) cell line L1236. Examination of the 15-LOX-1 5' promoter region demonstrated three putative binding sites for signal transducer and activator of transcription (STAT6) within the proximal 1200 base pairs relative to the start codon. Analysis by serial promoter deletions and STAT6 binding site mutations indicated that all three STAT6 binding sites are required for full activation of the 15-LOX-1 promoter. Chromatin immunoprecipitation assay demonstrated that these regions were occupied by STAT6 in L1236 (15-LOX-1 positive) but not in L428 (15-LOX-1 negative) cultured HL cells. Furthermore, DNA hypomethylation and histone hyperacetylation were detectable within the core promoter region of 15-LOX-1 only in L1236 cells but not L428 cells. Taken together, our data indicate that STAT6 activation and chromatin remodeling by DNA demethylation and histone acetylation are crucial for transcriptional activation of 15-LOX-1 in cultured HL cells. These prerequisites are fulfilled in the L1236 cell line, but not in the L428 cell line.