Human 5-lipoxygenase regulates transcription by association to euchromatin

Biochem Pharmacol. 2022 Sep;203:115187. doi: 10.1016/j.bcp.2022.115187. Epub 2022 Jul 22.


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, besides its canonical function as an arachidonic acid metabolizing enzyme, is a regulator of gene expression associated with euchromatin. By Crispr-Cas9-mediated 5-LO knockout (KO) in MonoMac6 (MM6) cells and subsequent RNA-Seq analysis, we identified 5-LO regulated genes which could be clustered to immune/defense response, cell adhesion, transcription and growth/developmental processes. Analysis of differentially expressed genes identified cyclooxygenase-2 (COX2, PTGS2) and kynureninase (KYNU) as strongly regulated 5-LO target genes. 5-LO knockout affected MM6 cell adhesion and tryptophan metabolism via inhibition of the degradation of the immunoregulator kynurenine. By subsequent FAIRE-Seq and 5-LO ChIP-Seq analyses, we found an association of 5-LO with euchromatin, with prominent 5-LO binding to promoter regions in actively transcribed genes. By enrichment analysis of the ChIP-Seq results, we identified potential 5-LO interaction partners. Furthermore, 5-LO ChIP-Seq peaks resemble patterns of H3K27ac histone marks, suggesting that 5-LO recruitment mainly takes place at acetylated histones. In summary, we demonstrate a noncanonical function of 5-LO as transcriptional regulator in monocytic cells.

Keywords: 5-lipoxygenase; ChIP-Seq; FAIRE-Seq; RNA-Seq; Transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonate 15-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase* / genetics
  • Arachidonate 5-Lipoxygenase* / metabolism
  • Euchromatin* / genetics
  • Histones / metabolism
  • Humans
  • Lipid Metabolism
  • Lipoxygenase / genetics
  • Lipoxygenase / metabolism


  • Euchromatin
  • Histones
  • Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Arachidonate 5-Lipoxygenase