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| Subject Categories: Signal Transduction | Cellular Metabolism |
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| The EMBO Journal
(2008) 27, 1017–1028, doi:10.1038/emboj.2008.51 Published online 20 March 2008 |
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| Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks |
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| Sarah K Knutson1, Brenda J Chyla1, 5, Joseph M Amann1, 2, Srividya Bhaskara1, Stacey S Huppert3 and Scott W Hiebert1, 4 |
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1 Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA 2 Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, USA 3 Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA 4 Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA To whom correspondence should be addressed Scott W Hiebert, Department of Biochemistry, Vanderbilt University School of Medicine, 512 Preston Research Building, 23rd and Pierce Avenue, Nashville, TN 37232, USA. Tel.: +1 615 936 3582; Fax: +1 615 936 1790; E-mail: scott.hiebert@vanderbilt.edu 5 Present address: Abbott Laboratories, Abbott Park, IL, USA Received 5 February 2008; Accepted 25 February 2008; Published online 20 March 2008. |
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| Abstract |
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Histone deacetylase 3 (Hdac3) is an enzymatic component of transcriptional repression complexes recruited by the nuclear hormone receptors. Inactivation of Hdac3 in cancer cell lines triggered apoptosis, and removal of Hdac3 in the germ line of mice caused embryonic lethality. Therefore, we deleted Hdac3 in the postnatal mouse liver. These mice developed hepatomegaly, which was the result of hepatocyte hypertrophy, and these morphological changes coincided with significant imbalances between carbohydrate and lipid metabolism. Loss of Hdac3 triggered changes in gene expression consistent with inactivation of repression mediated by nuclear hormone receptors. Loss of Hdac3 also increased the levels of Ppar 2, and treatment of these mice with a Ppar antagonist partially reversed the lipid accumulation in the liver. In addition, gene expression analysis identified mammalian target of rapamycin signalling as being activated after deletion of Hdac3, and inhibition by rapamycin affected the accumulation of neutral lipids in Hdac3-null livers. Thus, Hdac3 regulates metabolism through multiple signalling pathways in the liver, and deletion of Hdac3 disrupts normal metabolic homeostasis. |
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| Keywords: chromatin, Hdac3, histone acetylation, metabolism |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHLiver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks The EMBO Journal Article Nature Medicine Article (01 Mar 2001) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore Nature Letters to Editor (29 Jan 2004) The STAT3 isoforms α and β have unique and specific functions Nature Immunology Article (01 Apr 2004) |
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