NsdD-mediated conserved and divergent gene regulatory networks in Aspergillus

NsdD-mediated conserved and divergent gene regulatory networks in Aspergillus

Heungyun Moon1,2,3, Mi-Kyung Lee4, Nancy P. Keller1,5, Hee-Soo Park6, Kap-Hoon Han7, Jae-Hyuk Yu2
1Department of Plant Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA, 2Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA, 3Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, Wisconsin, USA, 4Biological Resource Center/Korean Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea, 5Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA, 6School of Food Science and Biotechnology, Kyungpook National University, Daegu, Republic of Korea, 7Department of Pharmaceutical Engineering, Woosuk University, Wanju, Republic of Korea

NsdD is a global transcription factor which has a conserved GATA-type zinc finger domain that governs development and secondary metabolism in Aspergillus. However, its species-specific regulatory mechanisms remain unclear. Using network-based multiomics analyses in Aspergillus nidulans and Aspergillus flavus, we show that NsdD functions in a cell type– and species-dependent manner. Cross-complementation of A. flavus ΔnsdD with the A. nidulans nsdD gene partially rescued developmentaland transcriptional defects, indicating evolutionary divergence of function. Genome-wide ChIP-seq identified 502 direct NsdD targets in A. nidulans and 674 in A. flavus, including key developmental and metabolic regulators. A conserved binding motif (5′-GATCT-3′) was defined as the NsdD response element. Network reconstruction revealed conserved core modules but extensive regulatory rewiring between species, contributing to differences in asexual/sexual morphology and sterigmatocystin/aflatoxin biosynthesis. These findings provide the first comparative map of NsdD-mediated gene
regulatory networks in filamentous fungi and highlight how evolutionary changes enable a conserved TF to acquire species-specific roles.