Bachleitner Simone, Sørensen Jens Laurids, Gacek-Matthews Agnieszka, Sulyok Michael, Studt Lena, Strauss Joseph
Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna (BOKU), Vienna, Austria.
Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg, Denmark.
Front Microbiol. 2019 Aug 13;10:1759. doi: 10.3389/fmicb.2019.01759. eCollection 2019.
Fungi produce a plethora of secondary metabolites (SMs) involved in cellular protection, defense, and signaling. Like other metabolic processes, transcription of SM biosynthesis genes is tightly regulated to prevent an unnecessary use of resources. Genes involved in SM biosynthesis are usually physically linked, arranged in secondary metabolite gene clusters (SMGCs). Research over the last decades has shown that chromatin structure and posttranslational modifications (PTMs) of histones represent important layers of SMGC regulation. For instance, trimethylation of histone H3 lysine 4 (H3K4me3) is a PTM typically associated with promoter regions of actively transcribed genes. Previously, we have shown that the H3K4me3-specific, JmjC domain-containing histone demethylase KdmB functions not only in repression but also in activation of secondary metabolism in , suggesting that KdmB has additional functions apart from histone demethylation. In this study, we identified demethylase-independent functions of KdmB in transcriptional regulation of SM gene clusters. Furthermore, we show that this activating and demethylase-independent role of the H3K4 demethylase is also conserved in the phytopathogenic fungus . Lack of FgKdm5 resulted in significant downregulation of five of seven analyzed SMs, whereby only one SMGC depends on a functional JmjC-domain. In strains deficient in H3K4 methylation, i.e., ∆, largely phenocopied ∆, while this is not the case for most of the SMs analyzed in spp. Notably, KdmB could not rescue the demethylase function in ∆ but restored all demethylase-independent phenotypes.
真菌产生大量参与细胞保护、防御和信号传导的次级代谢产物（SMs）。与其他代谢过程一样，SM生物合成基因的转录受到严格调控，以避免资源的不必要消耗。参与SM生物合成的基因通常在物理上是相连的，排列在次级代谢产物基因簇（SMGCs）中。过去几十年的研究表明，染色质结构和组蛋白的翻译后修饰（PTMs）是SMGC调控的重要层面。例如，组蛋白H3赖氨酸4的三甲基化（H3K4me3）是一种通常与活跃转录基因启动子区域相关的PTM。此前，我们已经表明，具有H3K4me3特异性、含JmjC结构域的组蛋白去甲基化酶KdmB不仅在抑制中起作用，而且在激活次级代谢中也起作用，这表明KdmB除了组蛋白去甲基化之外还有其他功能。在本研究中，我们鉴定了KdmB在SM基因簇转录调控中不依赖去甲基化酶的功能。此外，我们表明这种H3K4去甲基化酶的激活和不依赖去甲基化酶的作用在植物病原真菌中也保守存在。缺乏FgKdm5导致所分析的7种SMs中的5种显著下调，其中只有一个SMGC依赖于功能性的JmjC结构域。在H3K4甲基化缺陷的菌株中，即∆，在很大程度上表现出与∆相似的表型，而在所分析的大多数SMs中，spp.并非如此。值得注意的是，KdmB不能挽救∆中的去甲基化酶功能，但恢复了所有不依赖去甲基化酶的表型。
