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Molecular and Cellular Biology, April 2007, p. 2758-2764, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.02334-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Developmental Changes in Histone macroH2A1-Mediated Gene Regulation{triangledown} ,{dagger}

Lakshmi N. Changolkar, Carl Costanzi, N. Adrian Leu, Dannee Chen, K. John McLaughlin, and John R. Pehrson*

Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Received 14 December 2006/ Accepted 5 January 2007

macroH2A histone variants have been implicated to function in gene silencing by several studies, including ones showing a preferential association of macroH2A on the inactive X chromosome. To examine macroH2A function in vivo, we knocked out macroH2A1. macroH2A1 knockout mice are viable and fertile. A broad screen of liver gene expression showed no evidence of defects in X inactivation but did identify genes that have increased expression levels in macroH2A1 knockouts. macroH2A1-containing nucleosomes are enriched on the coding and/or upstream regions of these genes, suggesting that their increased expression levels are a direct effect of the absence of macroH2A1. The concentrations of macroH2A1 nucleosomes on these genes are low in the livers of newborn mice, and the macroH2A1 knockout had little effect on the expression levels of these genes in newborn liver. Our results indicate that an increase in liver macroH2A1 during the transition from newborn to young-adult status contributes to a decrease in the expression levels of these genes. These genes cluster in the area of lipid metabolism, and we observed metabolic effects in macroH2A1 knockouts. Our results indicate that the function of macroH2A1 histones is not restricted to gene silencing but also involves fine tuning the expression of specific genes.

* Corresponding author. Mailing address: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104. Phone: (215) 898-0454. Fax: (215) 573-5189. E-mail: pehrson{at}vet.upenn.edu.

{triangledown} Published ahead of print on 22 January 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, April 2007, p. 2758-2764, Vol. 27, No. 7
0270-7306/07/$08.00+0     doi:10.1128/MCB.02334-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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  • Bernstein, E., Muratore-Schroeder, T. L., Diaz, R. L., Chow, J. C., Changolkar, L. N., Shabanowitz, J., Heard, E., Pehrson, J. R., Hunt, D. F., Allis, C. D. (2008). A phosphorylated subpopulation of the histone variant macroH2A1 is excluded from the inactive X chromosome and enriched during mitosis. Proc. Natl. Acad. Sci. USA 105: 1533-1538 [Abstract] [Full Text]  
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