Human 5-lipoxygenase regulates transcription by association to euchromatin [FAIRE-seq]

Human 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis, mostly expressed in leukocytes and thus a crucial component of the innate immune system. In this study, we show that 5-LO, beside its canonical function as a metabolizing enzyme, is also a regulator of gene expression in the monocytic cell line Mono Mac 6 (MM6). Using RNA-Seq, we identified 5-LO regulated genes which could be clustered to several biological functions, e.g. immune/defense response, cell adhesion, transcription and growth/developmental processes. Thereby, the majority of genes were upregulated by 5-LO KO. By conducting a ChIP-Seq analysis, we proved an association of 5-LO to DNA. In summary, we demonstrate an additional noncanonical function of 5-LO as a direct transcriptional regulator in MM6 cells that presumably regulates specific genes in dependence on histone acetylation. Three independent replicates of Formaldehyde Assisted Isolation of Regulatory Elemens (FAIRE)-Seq from MonoMac 6 cells (MM6) with and without 5-Lipoxygenase knockout after 72h treatment with TGF-β/1,25(OH)2D3 and with or without 2h LPS stimulation.