Submitted on December 28, 2006
Revised on February 2, 2007
Accepted on February 4, 2007
Differential gene expression of Caenorhabditis elegans on unmethylated and 4
-methyl sterols
Mark Merris, Tongsheng Wang, Patricia Soteropoulos, and John Lenard
Physiology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854
Corresponding Author: lenard{at}umdnj.edu
Transcriptional profiles of Caenorhabditis elegans grown on unmethylated sterols (desMSs) or on 4a-methylsterols (4MSs) were compared using microarrays. Thirty-four genes were up-regulated and two down-regulated >2-fold by growth on 4MSs, including 13 cuticle collagen (col) genes, 1 cuticlin gene (cut-1), 2 groundhog-like (grl) genes and 1 groundhog gene (grd-4); col-36 and grl-20 were 12- and 19-fold elevated, respectively. 15 of these 17 genes are assigned by Kim et al. (2001) 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 co-regulation. Of 6 additional grl genes, only grl-3 was up-regulated on lophenol, the rest down-regulated; cyclic 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 down-regulation in lophenol by RT-PCR. Expression of the insulin-like receptor daf-2 was lower in lophenol, while 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.
