Intrinsic Epigenetic Factors Cooperate with the Steroid Hormone Ecdysone to Govern Dendrite Pruning in Drosophila

Abstract

Pruning that selectively removes unnecessary axons/dendrites is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, dendritic arborization sensory neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone. However, it is unknown whether epigenetic factors are involved in dendrite pruning. Here, we analyzed 81 epigenetic factors, from which a Brahma (Brm)-containing chromatin remodeler and a histone acetyltransferase CREB-binding protein (CBP) were identified for their critical roles in initiating dendrite pruning. Brm and CBP specifically activate a key ecdysone response gene, sox14, but not EcR-B1. Furthermore, the HAT activity of CBP is important for sox14 expression and dendrite pruning. EcR-B1 associates with CBP in the presence of ecdysone, which is facilitated by Brm, resulting in local enrichment of an active chromatin mark H3K27Ac at the sox14 locus. Thus, specific intrinsic epigenetic factors cooperate with steroid hormones to activate selective transcriptional programs, thereby initiating neuronal remodeling.