TY  - JOUR
A1  - Kreiß, Marius
A1  - Oberlis, Julia H.
A1  - Seuter, Sabine
A1  - Bischoff-Kont, Iris
A1  - Sürün, Duran
A1  - Thomas, Dominique Jeanette
A1  - Göbel, Tamara
A1  - Schmid, Tobias
A1  - Rådmark, Olof
A1  - Brandes, Ralf
A1  - Fürst, Robert
A1  - Häfner, Ann-Kathrin
A1  - Steinhilber, Dieter
T1  - Human 5-lipoxygenase regulates transcription by association to euchromatin
T2  - Biochemical Pharmacology
N2  - 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.
KW  - 5-lipoxygenase
KW  - RNA-Seq
KW  - ChIP-Seq
KW  - FAIRE-Seq
KW  - Transcriptional regulation
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/78404
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-784047
SN  - 0006-2952
VL  - 203
IS  - 115187
PB  - Elsevier
CY  - Amsterdam
ER  -