In bees from genus Melipona, differential feeding is not enough to fully explain female polyphenism. In these bees, there is a hypothesis that in addition to the environmental component (food), a genetic component is also involved caste differentiation regulation. This mechanism has not yet been fully elucidated and may involve epigenetic and metabolic regulation. Here, we analysed the expression of the genes encoding histone deacetylases HDAC1 and HDAC4 and histone acetyltransferase KAT2A in Melipona scutellaris. We also investigated the metabolic profile of larvae and larval food to search for putative queen-fate inducing compounds. Finally, we assessed the effect of the histone deacetylase inhibitor 10-hydroxy-2E-decenoic acid (10HDA) - the major lipid component of royal jelly and hence a putative regulator of honeybee caste differentiation - on Melipona caste differentiation. The hdac1, hdac4 and kat2a transcripts were expressed at all stages, with fluctuations in developmental stages and castes, which may be related to endocrine regulation. We did not identify the putative caste-differentiation factors, geraniol and 10HDA. Also, 10HDA was unable to promote differentiation in queens. Our results suggest that epigenetic and hormonal regulations act synergistically for drive caste differentiation in Melipona and that 10HDA is not a caste-differentiation factor in Melipona scutellaris.