Bacterium-triggered remodeling of chromatin identifies BasR, a novel regulator of fungal natural product biosynthesis

Fischer, J.; Müller, S.; Gacek-Matthews, A.; Netzker, T.; Jäger, N.; Scherlach, K.; Stroe, M. C.; Garcia-Altares, M.; Pezzini, F.; Schoeler, H.; Reichelt, M.; Gershenzon, J.; Krespach, M. K. C.; Shelest, E.; Schroeckh, V.; Valiante, V.; Heinzel, T.; Hertweck, C.; Strauss, J.; Brakhage, A. A.

doi:10.1101/211979

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bioRxiv · 10.1101/211979

Bacterium-triggered remodeling of chromatin identifies BasR, a novel regulator of fungal natural product biosynthesis

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Abstract

The eukaryotic epigenetic machinery is targeted by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. In line, we discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster leading to the production of orsellinic acid in the fungus Aspergillus nidulans. Using this model we aim at understanding molecular mechanisms of communication between bacteria and eukaryotic microorganisms based on bacteria-triggered chromatin modification. By genome-wide ChIP-seq analysis of acetylated histone H3 (H3K9ac, H3K14ac) we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus. Genome-wide acetylation of H3K9 correlated with increased gene expression, whereas H3K14 appears to function in transcriptional initiation by providing a docking side for regulatory proteins. In total, histones belonging to six secondary metabolism gene clusters showed higher acetylation during co-cultivation including the ors, aspercryptin, cichorine, sterigmatocystin, anthrone and 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde gene cluster with the emericellamide cluster being the only one with reduced acetylation and expression. Differentially acetylated histones were also detected in genes involved in amino acid and nitrogen metabolism, signaling, and genes encoding transcription factors. In conjunction with LC-MS/MS and MALDI-MS imaging, molecular analyses revealed the cross-pathway control and Myb-like transcription factor BasR as regulatory nodes for transduction of the bacterial signal in the fungus. The presence of basR in other fungal species allowed forecasting the inducibility of ors-like gene clusters by S. rapamycinicus in these fungi, and thus their effective interaction with activation of otherwise silent gene clusters.

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Fischer, J., Müller, S., Gacek-Matthews, A., Netzker, T., Jäger, N., Scherlach, K., Stroe, M. C., Garcia-Altares, M., Pezzini, F., Schoeler, H., Reichelt, M., Gershenzon, J., Krespach, M. K. C., Shelest, E., Schroeckh, V., Valiante, V., Heinzel, T., Hertweck, C., Strauss, J., Brakhage, A. A.. 2017-10-31. Bacterium-triggered remodeling of chromatin identifies BasR, a novel regulator of fungal natural product biosynthesis. https://doi.org/10.1101/211979

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