Histone modifications and skeletal muscle metabolic gene expression

McGee, Sean L. and Hargreaves, Mark 2010, Histone modifications and skeletal muscle metabolic gene expression, Clinical and experimental pharmacology and physiology, vol. 37, no. 3, pp. 392-396, doi: 10.1111/j.1440-1681.2009.05311.x.

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Title Histone modifications and skeletal muscle metabolic gene expression
Author(s) McGee, Sean L.ORCID iD for McGee, Sean L. orcid.org/0000-0001-6953-106X
Hargreaves, Mark
Journal name Clinical and experimental pharmacology and physiology
Volume number 37
Issue number 3
Start page 392
End page 396
Total pages 5
Publisher Wiley - Blackwell Publishing Asia
Place of publication Richmond, Vic.
Publication date 2010-03
ISSN 0305-1870
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.
Language eng
DOI 10.1111/j.1440-1681.2009.05311.x
Field of Research 060114 Systems Biology
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2010
Persistent URL http://hdl.handle.net/10536/DRO/DU:30025039

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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Created: Fri, 12 Mar 2010, 12:09:50 EST by Sean McGee

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