Clusters of biotin-responsive genes in human peripheral blood mononuclear cells.
Effects of biotin in cell signaling are mediated by transcription factors such as nuclear factor-kappa B (NF-kappa B) and Sp1/Sp3 as well as by posttranslational modifications of DNA-binding proteins. These signaling pathways play roles in the transcriptional regulation of numerous genes. Here we tested the hypothesis that biotin-dependent genes are not randomly distributed in the human genome but are arranged in clusters. Peripheral blood mononuclear cells were isolated from healthy adults before and after supplementation with 8.8 micromol/day biotin for 21 days. Cells were cultured ex vivo with concanavalin A for 3 hours to stimulate gene expression. Abundances of mRNA encoding approximately 14,000 genes were quantified by both DNA microarray and reverse transcriptase-polymerase chain reaction. The expression of 139 genes increased by at least 40% in response to biotin supplementation, whereas the expression of 131 genes decreased by at least 40% in response to biotin supplementation. The following clusters of biotin-responsive genes were identified: 1) 16% of biotin-responsive gene products localized to the cell nucleus; at least 28% of biotin-responsive genes play roles in signal transduction (these findings are consistent with a role for biotin in cell signaling); and 2) of the biotin-responsive genes, 54% clustered on chromosomes 1, 2, 3, 11, 12, and 19, whereas no biotin-responsive genes were found on chromosomes 10, 16, 18, 21, and heterosomes. This suggests that position effects play a role in biotin-dependent gene expression. Collectively, these findings suggest that the human genome contains clusters of biotin-dependent genes.
Wiedmann
Silke
S
Department of Nutrition and Health Sciences, University of Nebraska at Lincoln, 316 Ruth Leverton Hall, Lincoln, NE 68583-0806, USA.
Rodriguez-Melendez
Rocio
R
Ortega-Cuellar
Daniel
D
Zempleni
Janos
J
D000328:Adult; D001710:Biotin / Q000097:blood / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
D003208:Concanavalin A; D001710:Biotin