Project description: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.
Project description: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.
Project description: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.
Project description:The nature of chromatin as regular succession of nucleosomes has gained iconic status. The average nucleosome repeat length (NRL) determined by classical means serves as index for bulk chromatin of a given specimen. However, this value is dominated by regular heterochromatin since nucleosomal arrays are often not regular at individual single copy sequences. To obtain a measure for nucleosome regularity in euchromatin we subjected nucleosome dyad profiles to autocorrelation and spectral density analyses. This revealed variation in nucleosome regularity and NRL at different types of euchromatin and yielded a comprehensive catalog of regular phased nucleosome arrays (PNA). The absence of the nucleosome sliding factor ACF1 correlated with global loss of regularity in euchromatin and increased NRL and compromised phasing at a novel type of PNA. Our approach is generally applicable to characterize hallmarks of euchromatin organization.
Project description:The nature of chromatin as regular succession of nucleosomes has gained iconic status. The average nucleosome repeat length (NRL) determined by classical means serves as index for bulk chromatin of a given specimen. However, this value is dominated by regular heterochromatin since nucleosomal arrays are often not regular at individual single copy sequences. To obtain a measure for nucleosome regularity in euchromatin we subjected nucleosome dyad profiles to autocorrelation and spectral density analyses. This revealed variation in nucleosome regularity and NRL at different types of euchromatin and yielded a comprehensive catalog of regular phased nucleosome arrays (PNA). The absence of the nucleosome sliding factor ACF1 correlated with global loss of regularity in euchromatin and increased NRL and compromised phasing at a novel type of PNA. Our approach is generally applicable to characterize hallmarks of euchromatin organization.