2-Bromopalmitate modulates neuronal differentiation through the regulation of histone acetylation

• 2BP, a protein palmitoylation inhibitor, impairs neuronal differentiation.
• 2BP reduces histones H3 and H4 acetylation and inhibits cell cycle withdrawal.
• Palmitoylation modifies P300 and regulates neuronal differentiation cell events.

In order to evaluate the functional significance of palmitoylation during multi-potent neural stem/progenitor cell proliferation and differentiation, retinoic acid-induced P19 cells were used in this study as a model system. Cell behaviour was monitored in the presence of the protein palmitoylation inhibitor 2-bromopalmitate (2BP). Here, we observed a significant reduction in neuronal differentiation in the 2BP-treated cell model. We further explored the underlying mechanisms and found that 2BP resulted in the decreased acetylation of histones H3 and H4 and interfered with cell cycle withdrawal and neural stem/progenitor cells' renewal. Our results established a direct link between palmitoylation and the regulation of neural cell fate specification and revealed the epigenetic regulatory mechanisms that are involved in the effects of palmitoylation during neural development.