Temasek Life Sciences Laboratory and Department of Biological Sciences, 1 Research Link, National University of Singapore, Singapore 117604.
Neuron. 2011 Oct 6;72(1):86-100. doi: 10.1016/j.neuron.2011.08.003.
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.
选择性去除不必要的轴突/树突的修剪对于发育过程中神经回路的形成至关重要。在果蝇变态过程中，树突分枝感觉神经元 ddaC 会对蜕皮激素（ecdysone）做出反应，选择性地修剪其幼虫期的树突。然而，目前尚不清楚表观遗传因素是否参与树突修剪。在这里，我们分析了 81 种表观遗传因子，其中包含染色质重塑因子 Brm 和组蛋白乙酰转移酶 CREB 结合蛋白（CBP）的因子，对于启动树突修剪起着关键作用。Brm 和 CBP 特异性地激活关键的蜕皮激素反应基因 sox14，但不激活 EcR-B1。此外，CBP 的 HAT 活性对于 sox14 的表达和树突修剪很重要。EcR-B1 在存在蜕皮激素的情况下与 CBP 结合，这一过程由 Brm 促进，导致 sox14 基因座处的活性染色质标记 H3K27Ac 的局部富集。因此，特定的内在表观遗传因子与类固醇激素合作激活选择性转录程序，从而启动神经元重塑。
