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Papers In Press, published online ahead of print May 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600552-JLR200

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Journal of Lipid Research, Vol. 48, 1159-1166, May 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Differential gene expression of Caenorhabditis elegans grown on unmethylated sterols or 4-methylsterols

Mark Merris^1,*, Tongsheng Wang^1,, Patricia Soteropoulos and John Lenard^2,*

^* Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854
Center for Applied Genomics, Public Health Research Institute, Newark, NJ 07103

Published, JLR Papers in Press, February 4, 2007.

¹ M. Merris and T. Wang contributed equally to this work.

² To whom correspondence should be addressed. e-mail: lenard{at}umdnj.edu

Transcriptional profiles of Caenorhabditis elegans grown on unmethylated sterols (desMSs) or on 4-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were upregulated and 2 were downregulated >2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticulin gene (cut-1), 2 groundhog-like (grl) genes, and 1 groundhog gene (grd-4); col-36 and grl-20 were increased 12- and 19-fold, respectively. Fifteen of these 17 genes have been assigned to metabolic mountain 17, suggesting coordinate 4MS-mediated regulation of expression. Quantitative RT-PCR was performed on 27–51 h old animals grown on cholesterol (a desMS) or lophenol (a 4MS). col-36 and grl-20 showed similar cyclic peaks of expression in cholesterol and similar alterations in lophenol, suggesting coregulation. Of six additional grl genes, only grl-3 was upregulated on lophenol; the rest were downregulated. Cyclicity of expression was lost or altered in all six. Nuclear receptor genes nhr-23, nhr-25, nhr-41, and daf-12 all showed cyclic expression in cholesterol and significant downregulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2 was lower in lophenol, whereas that of its major downstream target daf-16 was higher. Thus, major changes in gene expression accompany growth on 4MSs, but with surprisingly little effect on normal growth and development.

Supplementary key words transcription • reverse transcription polymerase chain reaction • microarray • cholesterol • lathosterol • lophenol • 4-methyl-5-cholest-8(14)-en-3ß-ol • larval development

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