Bastakis Emmanouil, Gerke Jennifer, Özkan Seyma, Harting Rebekka, Lienard Tanja, Sasse Christoph, Xylakis Emmanouil S, Aden Merle, Strohdiek Anja, Heinrich Gabriele, Grosse Verena, Braus Gerhard H
Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, University of Göttingen, Göttingen, Germany.
PLoS Genet. 2025 Jul 17;21(7):e1011578. doi: 10.1371/journal.pgen.1011578. eCollection 2025 Jul.
Development and secondary metabolism of the filamentous fungus Aspergillus nidulans are tightly controlled by concerted actions of several master regulator transcription factors (TFs). The connection between fungal development and cellular stress response programs is often elusive. Here we show that the zinc finger TF MsnA, which controls salt-stress response, is a novel major regulator of fungal development. A molecular circuit among MsnA and the velvet domain regulator VelB was discovered, which mutually fosters the actions of both regulatory proteins during development. Chromatin immunoprecipitation coupled with next generation sequencing (ChIP-seq) and gene expression studies have revealed that MsnA controls the expression of several genes encoding key transcriptional regulators of asexual as well as sexual development. The double mutant of msnA with velB showed that both genes share an additive genetic relationship, under normal and salt stress conditions, with each protein to control distinct phenotypical features. In addition, MsnA directly and indirectly affects the synthesis of specific secondary metabolites relevant for fungal defense against other organisms and growth, in addition to salt-stress responses. Moreover, the expression of genes encoding the epigenetic regulators VapA, VipC and LaeA are also directly controlled by MsnA. The VapA-VipC-VapB methyltransferase signal transduction complex promotes asexual differentiation, while the VeA-VelB-LaeA complex balances light response, development and the secondary metabolism of the fungus. MsnA is therefore placed at a novel prominent position of the central regulatory network, which coordinates stress responses with the developmental and metabolic fate of the fungus.
丝状真菌构巢曲霉的发育和次生代谢受到几种主要调节转录因子（TFs）协同作用的严格控制。真菌发育与细胞应激反应程序之间的联系常常难以捉摸。在此，我们表明控制盐胁迫反应的锌指TF MsnA是真菌发育的一种新型主要调节因子。发现了MsnA与天鹅绒结构域调节因子VelB之间的分子回路，在发育过程中二者相互促进对方的作用。染色质免疫沉淀结合下一代测序（ChIP-seq）和基因表达研究表明，MsnA控制着几个编码无性和有性发育关键转录调节因子的基因的表达。msnA与velB的双突变体表明，在正常和盐胁迫条件下，这两个基因具有累加遗传关系，每种蛋白质控制不同的表型特征。此外，除了盐胁迫反应外，MsnA还直接和间接影响与真菌抵御其他生物体和生长相关的特定次生代谢产物的合成。此外，编码表观遗传调节因子VapA、VipC和LaeA的基因的表达也直接受MsnA控制。VapA-VipC-VapB甲基转移酶信号转导复合体促进无性分化，而VeA-VelB-LaeA复合体平衡真菌的光反应、发育和次生代谢。因此，MsnA处于中央调控网络的一个新的显著位置，该网络协调应激反应与真菌的发育和代谢命运。
