Role of histone modification in 12‑lipoxygenase‑associated p21 gene regulation

The aim of the present study was to examine the impacts and mechanisms of 12‑lipoxygenase (12‑LO) and its metabolites on the acetylation and methylation of histone‑3‑lysine (H3K) in the p21 gene. Rat mesangial cells (MCs) were selected for use in the present study. A chromatin immunoprecipitation assay, reverse transcription‑quantitative polymerase chain reaction analysis and a luciferase assay were used to detect transcriptional activities, the acetylation (Ac) of H3K (H3KAc), p21 promoter methylation (Me) and the transcription regions induced by 12 (S)‑hydroxyeicosatetraenoic acid (HETE). The cells were transfected to induce the overexpression of p300 to examine changes in 12 (S)‑HETE‑associated p21 regulation and epigenetic modifications. 12 (S)‑HETE enhanced p21 transcriptional activity and mRNA expression. In the promoter regions, P1 and P2, and the T1 transcription region, 12 (S)‑HETE induced significant H3K9 Ac and H3K4 Me1 epigenetic modifications, however, no changes were observed in the T2 region. By contrast, 12 (S)‑HETE treatment markedly prevented H3K9Me3 at the p21 promoter, suggesting that complex Me was involved in 12 (S)‑HETE‑associated p21 regulation. Furthermore, the overexpression of p300 markedly enhanced basal and 12 (S)‑HETE‑associated p21 transcriptional regulation in the MCs. 12 (S)‑HETE treatment also induced histone acetyltransferase p300 occupancy in the p21 promoter, and reduced the nuclear expression and occupancy of lysine‑specific demethylase (LSD1) in the p21 promoter. 12 (S)‑HETE induced p300 occupancy, and reduced the nuclear expression and occupancy of LSD1 in the p21 promoter. Therefore, enhanced H3K9Ac and H3K4Me1 in the p21 promoter and transcription regions, and decreased H3K9Me3 in the p21 promoter increased the expression of p21.