Issue 12, 2009
From the journal:

Molecular BioSystems

A c-Myc regulatory subnetwork from human transposable element sequences†‡

Jianrong Wang,a   Nathan J. Bowen,b   Leonardo Mariño-Ramírezcd  and  I. King Jordan*a  

* Corresponding authors

a School of Biology, Georgia Institute of Technology, Atlanta, USA
E-mail: king.jordan@biology.gatech.edu, jwang64@gatech.edu

b School of Biology and Ovarian Cancer Institute, Georgia Institute of Technology, Atlanta, USA
E-mail: bowen@gatech.edu

c National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, USA
E-mail: lmarino@corpoica.org.co

d Computational Biology and Bioinformatics Unit, Bioindustry and Biotechnology Center, Corporación Colombiana de Investigación Agropecuaria – CORPOICA, Bogota, Colombia

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.

Graphical abstract: A c-Myc regulatory subnetwork from human transposable element sequences

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Article information

DOI
https://doi.org/10.1039/B908494K
Article type
Paper
Submitted
28 Apr 2009
Accepted
23 Jun 2009
First published
21 Jul 2009

Mol. BioSyst., 2009,5, 1831-1839

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A c-Myc regulatory subnetwork from human transposable element sequences

J. Wang, N. J. Bowen, L. Mariño-Ramírez and I. K. Jordan, Mol. BioSyst., 2009, 5, 1831 DOI: 10.1039/B908494K

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