Department of Biology, Drexel University, Philadelphia, PA, United States; Program in Molecular and Cellular Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA, United States.
Department of Biology, Drexel University, Philadelphia, PA, United States.
Mol Cell Neurosci. 2018 Mar;87:77-85. doi: 10.1016/j.mcn.2017.11.007. Epub 2017 Dec 15.
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.
我们开始理解表观遗传蛋白控制染色质动态的复杂机制，以紧密调控正常发育。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，我们证明了组蛋白去乙酰化酶（HDACs）的活性与果蝇肌神经接点（NMJ）中的染色质重塑酶相互拮抗。HDAC 功能的药理学抑制逆转了与 Kismet 相关的功能丧失表型，Kismet 是一种染色质解旋酶 DNA 结合（CHD）蛋白。抑制 HDACs 可抑制运动缺陷、NMJ 的过度生长以及与 Kismet 缺失相关的神经传递缺陷。我们假设 Kismet 和 HDACs 可能在神经系统中针对相似的一组靶基因。我们的结果进一步了解了体内表观遗传蛋白功能之间的复杂相互作用。
