Switching off the yeast-to-hyphae transition in Yarrowia lipolytica through histone deacetylase inhibitors.

Fungi can develop a variety of morphotypes to survive, colonize, adapt and prevail under different environmental conditions. In general, two morphological shapes encompass the others: yeast (unicellular) and hyphae (multicellular). Under specific conditions, some fungi can adopt these two cellular morphologies, and for this reason, they are called dimorphic. Histone acetylation and deacetylation are well-known important mechanisms of chromatin remodelling that control cell differentiation processes as dimorphism. The reactions involved are catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the present work, we used Yarrowia lipolytica as a dimorphic fungal model to investigate the effect of HDAC chemical inhibition on the growth and yeast-to-hyphae switch of fungi. For this purpose, we tested the compounds sodium butyrate (SB) and valproic acid (VPA) as epigenetic modulators. Our results indicated that Y. lipolytica tolerates high doses of these inhibitors due to its lipolytic nature. However, once the metabolic capability of the fungus is overcome, SB and VPA strongly suppress hyphal growth, suggesting that histone acetylation plays a pivotal role in the regulation of this process.