A c-Myc regulatory subnetwork from human transposable element sequences.
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.
Wang
Jianrong
J
School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA. jwang64@gatech.edu
Bowen
Nathan J
NJ
Mariño-Ramírez
Leonardo
L
Jordan
I King
IK
D001483:Base Sequence; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism; D004251:DNA Transposable Elements; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D015233:Models, Statistical; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D016415:Sequence Alignment
D004251:DNA Transposable Elements; D016271:Proto-Oncogene Proteins c-myc