Role of enok in epigenetic gene regulation in neural stem cell development in Drosophila melanogaster

Abstract

In humans, the acetyltransferase MOZ ( a.k.a MYST3 and KAT6A) and its paralog MORF (a.k.a MYST4 and KAT6B) are known to function in a complex containing BRPF1 as a scaffold protein. Both MOZ/MORF and BRPF1 are known to play essential roles in embryonic CNS development, stem cell maintenance and adult neurogenesis in vertebrates. However, the molecular mechanism for these functions and the CNS specific acetylation targets of this complex remain unknown. Here, I show, that the fly homolog of MOZ/MORF , enok (enoki mushroom) is necessary for maintenance of a specific subpopulation of neuroblasts, termed the type II neuroblasts in the larval central brain. We show that conversion of type II neuroblasts to type I neuroblast fate accounts for this loss and this function of enok is dependent on the activity of the HAT complex. Interestingly, overexpression of enok leads to type I neuroblast converting to type II neuroblast fate. overexpression of enok also results in supernumerary Dpn+ neuroblast like cells in both type I and type II neuroblast lineages suggesting that progeny of enok overexpressing NB fail to differentiate. By performing ChIP-Seq and qRT-PCR analysis we show that enok binds to pnt and btd (two genes previously known to be necessary in type II neuroblast maintenance) loci and positively regulates their expression. Overexpression of pnt in enok knockdown background rescued the loss of type II neuroblasts suggesting that enok maintains type II neuroblasts by positively regulating its targets.