Journal article
A HAT for sleep?: epigenetic regulation of sleep by Tip60 in Drosophila
Fly (Austin, Tex.), v 7(2), pp 99-104
Apr 2013
PMID: 23572111
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sleep disturbances are common in neurodegenerative diseases such as Alzheimer disease (AD). Unfortunately, how AD is mechanistically linked with interference of the body's natural sleep rhythms remains unclear. Our recent findings provide insight into this question by demonstrating that sleep disruption associated with AD is driven by epigenetic changes mediated by the histone acetyltransferase (HAT) Tip60. In this study, we show that Tip60 functionally interacts with the AD associated amyloid precursor protein (APP) to regulate axonal growth of Drosophila small ventrolateral neuronal (sLNv) pacemaker cells, and their production of neuropeptide pigment dispersing factor (PDF) that stabilizes appropriate sleep-wake patterns in the fly. Loss of Tip60 HAT activity under APP neurodegenerative conditions causes decreased PDF production, retraction of the sLNv synaptic arbor required for PDF release and disruption of sleep-wake cycles in these flies. Remarkably, excess Tip60 in conjunction with APP fully rescues these sleep-wake disturbances by inducing overelaboration of the sLNv synaptic terminals and increasing PDF levels, supporting a neuroprotective role for Tip60 in these processes. Our studies highlight the importance of epigenetic based mechanisms underlying sleep disturbances in neurodegenerative diseases like AD.
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Details
- Title
- A HAT for sleep?: epigenetic regulation of sleep by Tip60 in Drosophila
- Creators
- Sheila K Pirooznia - Department of Biology, Drexel University, Philadelphia, PA, USAFelice Elefant
- Publication Details
- Fly (Austin, Tex.), v 7(2), pp 99-104
- Publisher
- United States
- Grant note
- R01 HD057939 / NICHD NIH HHS R01HD057939 / NICHD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000323365800006
- Scopus ID
- 2-s2.0-84876217151
- Other Identifier
- 991014877794204721
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- Web of Science research areas
- Biochemistry & Molecular Biology