We are beginning to appreciate the complex mechanisms by which epigenetic proteins control chromatin dynamics to tightly regulate normal development. However, the interaction between these proteins, particularly in the context of neuronal function, remains poorly understood. Here, we demonstrate that the activity of histone deacetylases (HDACs) opposes that of a chromatin remodeling enzyme at the Drosophila neuromuscular junction (NMJ). Pharmacological inhibition of HDAC function reverses loss of function phenotypes associated with Kismet, a chromodomain helicase DNA-binding (CHD) protein. Inhibition of HDACs suppresses motor deficits, overgrowth of the NMJ, and defective neurotransmission associated with loss of Kismet. We hypothesize that Kismet and HDACs may converge on a similar set of target genes in the nervous system. Our results provide further understanding into the complex interactions between epigenetic protein function in vivo.

我们开始认识到表观遗传蛋白控制染色质动力学以严格调节正常发育的复杂机制。然而，这些蛋白质之间的相互作用，特别是在神经元功能的背景下，仍然知之甚少。在这里，我们证明了在果蝇中，组蛋白脱乙酰基酶（HDACs）的活性与染色质重塑酶的活性相反。神经肌肉接头（NMJ）。HDAC功能的药理学抑制作用可以逆转与Kismet有关的功能表型的丧失，Kismet是一种染色体域解旋酶DNA结合（CHD）蛋白。抑制HDAC可抑制运动功能障碍，NMJ过度生长以及与Kismet丧失相关的神经传递缺陷。我们假设Kismet和HDAC可能会收敛于神经系统中一组相似的靶基因。我们的结果提供了对体内表观遗传蛋白功能之间复杂相互作用的进一步理解。