Histone modifications and skeletal muscle metabolic gene expression

McGee, Sean L. and Hargreaves, Mark 2010, Histone modifications and skeletal muscle metabolic gene expression, in AuPS 2008 : Proceedings of the Australian Physiological Society Symposium: Signals Mediating Exercise-Induced Skeletal Muscle Remodelling, Wiley-Blackwell Publsihing Asia, Richmond, Vic., pp. 392-396.

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Title Histone modifications and skeletal muscle metabolic gene expression
Author(s) McGee, Sean L.
Hargreaves, Mark
Conference name Australian Physiological Society. Symposium (2008 : Melbourne, Vic.)
Conference location Melbourne, Vic.
Conference dates Dec. 2008
Title of proceedings AuPS 2008 : Proceedings of the Australian Physiological Society Symposium: Signals Mediating Exercise-Induced Skeletal Muscle Remodelling
Editor(s) [unknown]
Publication date 2010
Conference series Australian Physiological Society Symposium
Start page 392
End page 396
Total pages 5
Publisher Wiley-Blackwell Publsihing Asia
Place of publication Richmond, Vic.
Keyword(s) histone deacetylase
skeletal muscle
metabolism
intracellular signalling
histone modifications
Summary 1. Skeletal muscle oxidative function and metabolic gene expression are co-ordinately downregulated in metabolic diseases such as insulin resistance, obesity and Type 2 diabetes. Altering skeletal muscle metabolic gene expression to favour enhanced energy expenditure is considered a potential therapy to combat these diseases.
2. Histone deacetylases (HDACs) are chromatin-remodelling enzymes that repress gene expression. It has been shown that HDAC4 and 5 co-operatively regulate a number of genes involved in various aspects of metabolism. Understanding how HDACs are regulated provides insights into the mechanisms regulating skeletal muscle metabolic gene expression.
3. Multiple kinases control phosphorylation-dependent nuclear export of HDACs, rendering them unable to repress transcription. We have found a major role for the AMP-activated protein kinase (AMPK) in response to energetic stress, yet metabolic gene expression is maintained in the absence of AMPK activity. Preliminary evidence suggests a potential role for protein kinase D, also a Class IIa HDAC kinase, in this response.
4. The HDACs are also regulated by ubiquitin-mediated proteasomal degradation, although the exact mediators of this process have not been identified.
5. Because HDACs appear to be critical regulators of skeletal muscle metabolic gene expression, HDAC inhibition could be an effective therapy to treat metabolic diseases.
6. Together, these data show that HDAC4 and 5 are critical regulators of metabolic gene expression and that understanding their regulation could provide a number of points of intervention for therapies designed to treat metabolic diseases, such as insulin resistance, obesity and Type 2 diabetes.
ISSN 1440-1681
Language eng
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 920104 Diabetes
HERDC Research category E1.1 Full written paper - refereed
Related work DU:30025039
Persistent URL http://hdl.handle.net/10536/DRO/DU:30050753

Document type: Conference Paper
Collection: School of Medicine
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