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Constitutive Expression of the α10 Nicotinic Acetylcholine Receptor Subunit Fails to Maintain Cholinergic Responses in Inner Hair Cells After the Onset of Hearing

Tuning of the tectorial membrane in the basilar papilla of the northern leopard frog.

Spatial and temporal effects of interleaved masking in cochlear implants.

Lipid lateral mobility in cochlear outer hair cells: regional differences and regulation by cholesterol.

Year: 2009 Volume: 10 Issue: 2

Year: 2009 Volume: 10 Issue: 1

Epigenetic influences on sensory regeneration: histone deacetylases regulate supporting cell proliferation in the avian utricle.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Slattery, Eric L. Speck, Judith D. Warchol, Mark E.
Description	Country affiliation: United States Author Affiliation: Slattery EL ( Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA.)
Abstract	The sensory hair cells of the cochlea and vestibular organs are essential for normal hearing and balance function. The mammalian ear possesses a very limited ability to regenerate hair cells and their loss can lead to permanent sensory impairment. In contrast, hair cells in the avian ear are quickly regenerated after acoustic trauma or ototoxic injury. The very different regenerative abilities of the avian vs. mammalian ear can be attributed to differences in injury-evoked expression of genes that either promote or inhibit the production of new hair cells. Gene expression is regulated both by the binding of cis-regulatory molecules to promoter regions as well as through structural modifications of chromatin (e.g., methylation and acetylation). This study examined effects of histone deacetylases (HDACs), whose main function is to modify histone acetylation, on the regulation of regenerative proliferation in the chick utricle. Cultures of regenerating utricles and dissociated cells from the utricular sensory epithelia were treated with the HDAC inhibitors valproic acid, trichostatin A, sodium butyrate, and MS-275. All of these molecules prevent the enzymatic removal of acetyl groups from histones, thus maintaining nuclear chromatin in a 'relaxed' (open) configuration. Treatment with all inhibitors resulted in comparable decreases in supporting cell proliferation. We also observed that treatment with the HDAC1-, 2-, and 3-specific inhibitor MS-275 was sufficient to reduce proliferation and that two class I HDACs--HDAC1 and HDAC2--were expressed in the sensory epithelium of the utricle. These results suggest that inhibition of specific type I HDACs is sufficient to prevent cell cycle entry in supporting cells. Notably, treatment with HDAC inhibitors did not affect the differentiation of replacement hair cells. We conclude that histone deacetylation is a positive regulator of regenerative proliferation but is not critical for avian hair cell differentiation.
File Format	HTM / HTML
ISSN	15253961
e-ISSN	14387573
DOI	10.1007/s10162-009-0166-y
Journal	Journal of the Association for Research in Otolaryngology
Issue Number	3
Volume Number	10
Language	English
Publisher	Springer
Publisher Date	2009-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Otolaryngology Cell Proliferation Physiology Epigenesis, Genetic Histone Deacetylases Regeneration Saccule And Utricle Cytology Animals Apoptosis Drug Effects Benzamides Pharmacology Butyrates Cell Differentiation Cells, Cultured Epithelium Histone Deacetylase Inhibitors Hydroxamic Acids Pyridines Valproic Acid Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Otorhinolaryngology Sensory Systems

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Epigenetic Influences on Sensory Regeneration: Histone Deacetylases Regulate Supporting Cell Proliferation in the Avian Utricle

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