Functional Diversification of HMGB Proteins in Aspergillus nidulans: Linking Chromatin Architecture to Cellular Physiology and Development

High-mobility group box (HMGB) proteins are architectural chromatin-associated proteins that bind and bend DNA and facilitate interactions between chromatin and regulatory proteins. Despite their fundamental roles in eukaryotic chromatin, the functions of HMGB proteins remain poorly characterised in filamentous fungi. This review synthesises structural and functional studies of the three architectural HMGB proteins identified in the model fungus Aspergillus nidulans and highlights the remarkable functional diversification of this protein family. HmbA is a nuclear HMGB protein related to the Saccharomyces cerevisiae Nhp6A/Nhp6B architectural chromatin proteins and contributes to cell-wall remodelling, hyphal growth, germination, stress responses, and sexual development. HmbB is an unusual dual-localised nuclear and mitochondrial HMGB protein required for mitochondrial DNA maintenance, redox homeostasis, spore viability, and secondary metabolism. HmbC is structurally related to the S. cerevisiae HMGB-family protein Hmo1 and has a more specialised role in sexual development and functionally interacts with the global developmental regulator VeA. Despite these distinct functions, all three proteins contribute to normal mating-type gene expression and sexual reproduction. Collectively, these findings indicate that A. nidulans HMGB proteins have acquired specialised functions that connect chromatin-associated processes with cellular physiology, metabolism, and development. A. nidulans therefore provides a useful model for understanding how diversification within the HMGB family contributes to the regulation of complex biological processes in filamentous fungi.