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GNAT 家族组蛋白乙酰转移酶 Elp3 和 GcnE 在. 中的功能特征。

Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in .

机构信息

Department of Microbiology, Graduate School, Daejeon University, Daejeon 34520, Republic of Korea.

Department of Biomedical Laboratory Science, Daejeon University, Daejeon 34520, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Jan 22;24(3):2179. doi: 10.3390/ijms24032179.

Abstract

Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a pivotal role in the regulation of gene expression and diverse biological processes. However, the function of GNAT family HATs, especially Elp3, in the opportunistic human pathogenic fungus is largely unknown. To investigate the roles of the GNAT family HATs Elp3 and GcnE in the , we have generated and characterized individual null Δ and Δ mutants. The radial growth of fungal colonies was significantly decreased by the loss of or , and the number of asexual spores (conidia) in the Δ mutant was significantly reduced. Moreover, the mRNA levels of the key asexual development regulators were also significantly low in the Δ mutant compared to wild type (WT). Whereas both the Δ and Δ mutants were markedly impaired in the formation of adherent biofilms, the Δ mutant showed a complete loss of surface structure and of intercellular matrix. The Δ mutant responded differently to oxidative stressors and showed significant susceptibility to triazole antifungal agents. Furthermore, Elp3 and GcnE function oppositely in the production of secondary metabolites, and the Δ mutant showed attenuated virulence. In conclusion, Elp3 and GcnE are associated with diverse biological processes and can be potential targets for controlling the pathogenic fungus.

摘要

组蛋白乙酰转移酶(HATs)对染色质结构的翻译后修饰在基因表达和多种生物过程的调控中起着关键作用。然而,GNAT 家族 HATs,特别是 Elp3,在机会性病原体中的功能在很大程度上是未知的。为了研究 GNAT 家族 HATs Elp3 和 GcnE 在 中的作用,我们生成并表征了单个缺失 Δ 和 Δ 突变体。或缺失导致真菌菌落的径向生长显著降低,并且 Δ 突变体中的无性孢子(分生孢子)数量显著减少。此外,与野生型(WT)相比,Δ 突变体中关键无性发育调节剂的 mRNA 水平也显著降低。尽管 Δ 和 Δ 突变体在形成附着生物膜方面都明显受损,但 Δ 突变体显示出完全丧失表面结构和细胞间基质。Δ 突变体对氧化应激物的反应不同,并且对三唑类抗真菌药物表现出显著的敏感性。此外,Elp3 和 GcnE 在次生代谢产物的产生中具有相反的功能,并且 Δ 突变体的毒力减弱。总之,Elp3 和 GcnE 与多种生物过程相关,可作为控制致病真菌的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07ff/9916960/6bd1e406e702/ijms-24-02179-g001.jpg

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