Research Article: HMGB proteins are required for sexual development in Aspergillus nidulans

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Eszter Bokor, Judit Ámon, Kabichandra Keisham, Zoltán Karácsony, Csaba Vágvölgyi, Zsuzsanna Hamari, Kap-Hoon Han.


Aspergillus nidulans has three high mobility group box (HMGB) proteins, HmbA, HmbB and HmbC that are chromatin-associated architectural proteins involved in DNA-related functions. By creating and studying deletion strains in both veA+ and veA1 background, we have characterized the role of HmbA, HmbB and HmbC in sexual development. Expression of the mating-type MAT1-1 and MAT1-2 coding genes were found to be extremely down-regulated in all three mutants on day 4 of sexual development, which results in deficient ascospore production and/or ascospore viability in the mutants. In addition, we found that HmbA and HmbB play also a role in sensing of and response to environmental signals, while HmbC functionally interacts with VeA, a key regulator of the coordination of asexual and sexual development, as well as of secondary metabolism.

Partial Text

Beside linker histones (H1 and H5), B-type high mobility group box domain proteins (HMGB) (for nomenclature of HMG proteins see [1]) are also important architectural components of chromatin. These proteins can bind to linker DNA, and induce or repress gene expression. They are able to interact with both DNA and protein components of chromatin through their high mobility group box (HMG-box) domains (reviewed in [2–7]). The HMG-box domain (comprising three α-helices) folds up into an L-shape three dimensional form, and binds to the minor grove of DNA-helix, distorting the DNA’s backbone (reviewed in [4]). In HMGB proteins the amino acid that precedes the second α-helix of the HMG-box has non-polar characteristics, which endows the HMG-box with the ability to bind to the DNA with no or little sequence-specificity [3, 8]. HMGB proteins (e.g. human HMGB proteins, Drosophila DSP1, yeast HMO1 and HMO2) are generally composed of two or more copies of HMG-box domains, although single-copy HMG-box containing HMGB proteins also exist [4, 9, 10]. Three architectural HMGB proteins, namely HmbA (AN2885), HmbB (AN1267) and HmbC (AN10103), were identified in Aspergillus nidulans according to their diagnostic non-polar amino acids that precede the second α-helix in their canonical HMG-box [11]. Their closest characterized fungal homologues are Nhp6A/Bp, Abf2p and Hmo1p in Saccharomyces cerevisiae (homologues of HmbA, HmbB and HmbC, respectively) and mtHMG1 in Podospora anserina (homologue of HmbB) [9–15]. Of these three A. nidulans proteins, the physiological role of the dually localized mitochondrial/nuclear HmbB was previously characterized in details [11, 16]. Deletion of hmbB has pleiotropic effects (S1 Table). The hmbBΔ mutant is viable, but displays severe fitness loss due to the drastic reduction in the viability of conidiospores and ascospores (0.4% viable) [11]. Besides its role in spore viability, HmbB is also involved in diverse biological processes such as sugar metabolism during conidia germination, sterigmatocystin production, redox homeostasis or maintaining mitochondrial DNA copy number [11, 16]. The latter correlates with the mitochondrial localization of HmbB, whereas the other functions might be associated with the nuclear localization of the protein. This indicates that HmbB may play a role in the structure and function of nuclear chromatin [11]. This hypothesis is further supported by the altered transcription level of numerous nuclear genes in hmbBΔ [11, 16]. Regarding HmbA and HmbC, we have limited knowledge about their function in terms of their physiological roles and transcriptional regulation, however, based on the functions of their yeast homologues, it can be assumed that they modulate the expression of a wide range of genes [10, 14, 17, 18].

According to the results presented above, HmbA, HmbB and HmbC architectural chromatin components of A. nidulans are required for normal sexual development, especially for the formation and viability of ascospores and the spatial distribution of cleistothecia (Table 2, S1 Table). By studying hmbA, hmbB and hmbC deletions in both veA+ and veA1 background, we have investigated the possible functional interaction of these HMGB proteins with VeA, the master regulator of sexual development (Table 2, S1 Table).




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