A c-Myc regulatory subnetwork from human transposable element sequences

Mol Biosyst. 2009 Dec;5(12):1831-9. doi: 10.1039/B908494k. Epub 2009 Jul 21.

Abstract

Transposable elements (TEs) can donate regulatory sequences that help to control the expression of human genes. The oncogene c-Myc is a promiscuous transcription factor that is thought to regulate the expression of hundreds of genes. We evaluated the contribution of TEs to the c-Myc regulatory network by searching for c-Myc binding sites derived from TEs and by analyzing the expression and function of target genes with nearby TE-derived c-Myc binding sites. There are thousands of TE sequences in the human genome that are bound by c-Myc. A conservative analysis indicated that 816-4564 of these TEs contain canonical c-Myc binding site motifs. c-Myc binding sites are over-represented among sequences derived from the ancient TE families L2 and MIR, consistent with their preservation by purifying selection. Genes associated with TE-derived c-Myc binding sites are co-expressed with each other and with c-Myc. A number of these putative TE-derived c-Myc target genes are differentially expressed between Burkitt's lymphoma cells versus normal B cells and encode proteins with cancer-related functions. Despite several lines of evidence pointing to their regulation by c-Myc and relevance to cancer, the set of genes identified as TE-derived c-Myc targets does not significantly overlap with two previously characterized c-Myc target gene sets. These data point to a substantial contribution of TEs to the regulation of human genes by c-Myc. Genes that are regulated by TE-derived c-Myc binding sites appear to form a distinct c-Myc regulatory subnetwork.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / metabolism
  • DNA Transposable Elements*
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Humans
  • Models, Statistical
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • Regulatory Elements, Transcriptional*
  • Sequence Alignment

Substances

  • DNA Transposable Elements
  • Proto-Oncogene Proteins c-myc