Clusters of biotin-responsive genes in human peripheral blood mononuclear cells

Silke Wiedmann, Rocio Rodriguez-Melendez, Daniel Ortega-Cuellar, Janos Zempleni

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Effects of biotin in cell signaling are mediated by transcription factors such as nuclear factor-κB (NF-κB) 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 μmol/day biotin for 21 days. Cells were cultured ex vivo with concanavalin A for 3 hours to stimulate gene expression. Abundances of mRNA encoding ∼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.

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalJournal of Nutritional Biochemistry
Volume15
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • Biotin
  • DNA microarrays
  • Gene expression
  • Human
  • Peripheral blood mononuclear cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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