Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in <i>Beauveria bassiana</i>

Cai, Qing; Tong, Sen‐Miao; Shao, Wei; Ying, Sheng‐Hua; Feng, Ming‐Guang

doi:10.1111/cmi.12839

Cited by 26 publications

(42 citation statements)

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“…This observation is in accordance with results from yeast, where HOS2 was shown to shuttle between the cytoplasm and the nucleus via a chaperone dependent process ( Liu et al, 2012 ). Moreover, during the preparation of this manuscript, a paper was published that presented clear evidence that a HosA ortholog in the insect-pathogenic fungus Beauveria bassiana is indirectly involved in both, global acetylation and phosphorylation of H3K56 and H2AS129, respectively, providing further evidence of an indirect effect of HosA-type proteins in the regulation of fungal transcription via deacetylation of HATs or kinases ( Cai et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans

et al. 2018

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An outstanding feature of filamentous fungi is their ability to produce a wide variety of small bioactive molecules that contribute to their survival, fitness, and pathogenicity. The vast collection of these so-called secondary metabolites (SMs) includes molecules that play a role in virulence, protect fungi from environmental damage, act as toxins or antibiotics that harm host tissues, or hinder microbial competitors for food sources. Many of these compounds are used in medical treatment; however, biosynthetic genes for the production of these natural products are arranged in compact clusters that are commonly silent under growth conditions routinely used in laboratories. Consequently, a wide arsenal of yet unknown fungal metabolites is waiting to be discovered. Here, we describe the effects of deletion of hosA, one of four classical histone deacetylase (HDAC) genes in Aspergillus nidulans; we show that HosA acts as a major regulator of SMs in Aspergillus with converse regulatory effects depending on the metabolite gene cluster examined. Co-inhibition of all classical enzymes by the pan HDAC inhibitor trichostatin A and the analysis of HDAC double mutants indicate that HosA is able to override known regulatory effects of other HDACs such as the class 2 type enzyme HdaA. Chromatin immunoprecipitation analysis revealed a direct correlation between hosA deletion, the acetylation status of H4 and the regulation of SM cluster genes, whereas H3 hyper-acetylation could not be detected in all the upregulated SM clusters examined. Our data suggest that HosA has inductive effects on SM production in addition to its classical role as a repressor via deacetylation of histones. Moreover, a genome wide transcriptome analysis revealed that in addition to SMs, expression of several other important protein categories such as enzymes of the carbohydrate metabolism or proteins involved in disease, virulence, and defense are significantly affected by the deletion of HosA.

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Section: Discussionmentioning

confidence: 99%

A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans

et al. 2018

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“…This process has been evidently associated with the functions of many genes characterized in B. bassiana, such as those encoding the histone acetyltransferases Gcn5 and Mst2 (7, 9), the histone deacetylases Hos2 and Rpd3 (10, 11), the mitogen-activated protein kinase (MAPK) kinase Ste7 (12), the Na + /H + antiporter Nhx1 (13), the blue-light photoreceptor VVD (6), the vacuolar protein VLP4 (14) or ATPase subunit H VmaH (15), the lysyl-tRNA synthetase KRS (16), and the cyclophilin B CypB (17). Interestingly, these studied genes are also responsible for a correlation of dimorphic transition in vitro or in vivo with aerial conidiation and transcriptional activation of key activator genes in the central development pathway, as summarized in Table 1.…”

Section: Introductionmentioning

confidence: 99%

BrlA and AbaA Govern Virulence-Required Dimorphic Switch, Conidiation, and Pathogenicity in a Fungal Insect Pathogen

et al. 2019

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Dimorphic plant and human mycopathogens require a switch from the usual yeast growth to filamentous growth for host tissue penetration, and the switch is controlled by multiple signaling systems other than the central developmental pathway. Unlike these fungi, dimorphic insect mycopathogens usually grow by hyphal extension, infect the host by hyphal penetration through the insect cuticle, and switch to unicellular blastospores from the penetrating hyphae only after entry into the host hemocoel, where blastospore propagation by yeast-like budding accelerates host mummification. Here, we report a dependence of the virulence-required dimorphic transition on the central pathway activators BrlA and AbaA in Beauveria bassiana. Deletion of brlA or abaA abolished both aerial conidiation and submerged blastospore formation in vitro despite no negative impact on hyphal growth in various media, including a broth mimic of insect hemolymph. The hyphae of either deletion mutant lost insect pathogenicity through normal cuticle penetration, contrasting with a high infectivity of wild-type hyphae. The mutant hyphae injected into the host hemocoel failed to form blastospores, resulting in slower lethal action. Uncovered by transcriptomic analysis, several genes involved in host adhesion and cuticle degradation were sharply repressed in both deletion mutants versus wild type. However, almost all signaling genes homologous to those acting in the dimorphic switch of other fungi were not differentially expressed at a significant level and hence unlikely to be involved in shutting down the dimorphic switch of each deletion mutant. Therefore, like aerial conidiation, the submerged dimorphic switch in vitro and in vivo is a process of asexual development governed by the two central pathway activators in B. bassiana. IMPORTANCE Dimorphic insect mycopathogens infect the host by hyphal penetration through the host cuticle and switch from the penetrating hyphae to unicellular blastospores after entry into the host hemocoel, where blastospore propagation by yeast-like budding accelerates host mummification to death. The fungal virulence-required dimorphic switch is confirmed as a process of asexual development directly regulated by BrlA and AbaA, two key activators of the central developmental pathway in an insect mycopathogen. This finding unveils a novel mechanism distinct from the control of the dimorphic switch by multiple signaling systems other than the central developmental pathway in dimorphic plant and human mycopathogens, which switch from the usual yeast growth to filamentous growth required for pathogenicity through host tissue penetration.

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“…Phenotype assays suggested that in A. niger FGSC A1279, HosA played the most important role in the phenotype, including hyphal growth, pigment accumulation, and spore count of eight histone deacetylases. In Beauveria bassiana , deletion of hos2 increased the sensitivity to oxidative stress and reduced conidiation capacity [33]. The synthesis of SMs and proteins involved in virulence and disease are significantly affected by the deletion of HosA [34].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to being linked to histone deacetylation, HosA may be responsible for other epigenetic modifications. In Beauveria bassiana , the histone deacetylase Hos2 plays an indirect role in acetylating H3-K56 and phosphorylating H2A-S129 [33].…”

Section: Discussionmentioning

confidence: 99%

The Histone Deacetylases HosA and HdaA Affect the Phenotype and Transcriptomic and Metabolic Profiles of Aspergillus niger

Pan

Wang

2019

Toxins

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Histone acetylation is an important modification for the regulation of chromatin accessibility and is controlled by two kinds of histone-modifying enzymes: histone acetyltransferases (HATs) and histone deacetylases (HDACs). In filamentous fungi, there is increasing evidence that HATs and HDACs are critical factors related to mycelial growth, stress response, pathogenicity and production of secondary metabolites (SMs). In this study, seven A. niger histone deacetylase-deficient strains were constructed to investigate their effects on the strain growth phenotype as well as the transcriptomic and metabolic profiles of secondary metabolic pathways. Phenotypic analysis showed that deletion of hosA in A. niger FGSC A1279 leads to a significant reduction in growth, pigment production, sporulation and stress resistance, and deletion of hdaA leads to an increase in pigment production in liquid CD medium. According to the metabolomic analysis, the production of the well-known secondary metabolite fumonisin was reduced in both the hosA and hdaA mutants, and the production of kojic acid was reduced in the hdaA mutant and slightly increased in the hosA mutant. Results suggested that the histone deacetylases HosA and HdaA play a role in development and SM biosynthesis in A. niger FGSC A1279. Histone deacetylases offer new strategies for regulation of SM synthesis.

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Pleiotropic effects of the histone deacetylase Hos2 linked to H4-K16 deacetylation, H3-K56 acetylation, and H2A-S129 phosphorylation in Beauveria bassiana

Cited by 26 publications

References 57 publications

A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans

A Class 1 Histone Deacetylase as Major Regulator of Secondary Metabolite Production in Aspergillus nidulans

BrlA and AbaA Govern Virulence-Required Dimorphic Switch, Conidiation, and Pathogenicity in a Fungal Insect Pathogen

The Histone Deacetylases HosA and HdaA Affect the Phenotype and Transcriptomic and Metabolic Profiles of Aspergillus niger

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