H4K5 deacetylation regulates cell wall integrity pathway in Saccharomyces cerevisiae exposed to nickel stress

Abstract:

[Objective] Nickel (Ni) is one of the heavy metal pollutants to which humans are widely exposed, and nickel exposure activates the cell wall integrity (CWI) signaling pathway, which lowers the level of intracellular histone acetylation. However, whether the CWI pathway is regulated by histone acetylation under nickel stress remains to be fully understood. [Methods] We used the histone-targeted mutant strain H4K5R (mimicking the deacetylated state) to study the regulation of the CWI pathway in Saccharomyces cerevisiae by H4K5 deacetylation under nickel stress, aiming to lay a foundation for unveiling the regulatory role of histone modifications in eukaryotes in response to heavy metal stress. [Results] Compared with the wildtype strain, H4K5R had strong nickel resistance, being able to grow in the presence of 5.0 mmol/L NiCl₂. The results of Western blotting and qRT-PCR showed that the CWI pathway of the wildtype strain BY4741 was activated under 5.0 mmol/L NiCl₂, with the expression of Mnn9 (encoding α-1,6-mannosyl transferase) and Fks1 (encoding glucan synthase) being up-regulated by 3.13 folds and 1.49 folds, respectively. Moreover, the content of mannan and β-glucan were increased, which indicated that the wildtype strain activated the CWI pathway to increase the content of cell wall component. The activation of the CWI pathway in H4K5R was mild under the stress of 5.0 mmol/L NiCl₂. Although the expression of Mnn9 and Fks1 was up-regulated, the changes in mannan content were not significant, and the increase in β-glucan content was less than that of the wildtype strain. [Conclusion] Under 5.0 mmol/L NiCl₂ stress, the deacetylation of H4K5 in the mutant strain regulated the CWI pathway, which affected the changes in cell wall components.