Article

Polak, P. & Domany, E. Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes. BMC Genomics 7, 133

Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel.
BMC Genomics (Impact Factor: 3.99). 02/2006; 7:133. DOI: 10.1186/1471-2164-7-133
Source: PubMed

ABSTRACT

The human genome contains over one million Alu repeat elements whose distribution is not uniform. While metabolism-related genes were shown to be enriched with Alu, in structural genes Alu elements are under-represented. Such observations led researchers to suggest that Alu elements were involved in gene regulation and were selected to be present in some genes and absent from others. This hypothesis is gaining strength due to findings that indicate involvement of Alu elements in a variety of functions; for example, Alu sequences were found to contain several functional transcription factor (TF) binding sites (BSs). We performed a search for new putative BSs on Alu elements, using a database of Position Specific Score Matrices (PSSMs). We searched consensus Alu sequences as well as specific Alu elements that appear on the 5 Kbp regions upstream to the transcription start site (TSS) of about 14000 genes.
We found that the upstream regions of the TSS are enriched with Alu elements, and the Alu consensus sequences contain dozens of putative BSs for TFs. Hence several TFs have Alu-associated BSs upstream of the TSS of many genes. For several TFs most of the putative BSs reside on Alu; a few of these were previously found and their association with Alu was also reported. In four cases the fact that the identified BSs resided on Alu went unnoticed, and we report this association for the first time. We found dozens of new putative BSs. Interestingly, many of the corresponding TFs are associated with early markers of development, even though the upstream regions of development-related genes are Alu-poor, compared with translational and protein biosynthesis related genes, which are Alu-rich. Finally, we found a correlation between the mouse B1 and human Alu densities within the corresponding upstream regions of orthologous genes.
We propose that evolution used transposable elements to insert TF binding motifs into promoter regions. We observed enrichment of biosynthesis genes with Alu-associated BSs of developmental TFs. Since development and cell proliferation (of which biosynthesis is an essential component) were proposed to be opposing processes, these TFs possibly play inhibitory roles, suppressing proliferation during differentiation.

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    • "Similarly, a large fraction of functional 217 genomic sites consists of primate-specific TEs derived from ERV1 (Wang, T. et al., 2007). In 218 addition, Alu and L2 elements contain TF binding motifs those expected to bind by TFs in 219 vivo (Johnson et al., 2006;Laperriere et al., 2007;Polak and Domany, 2006). Next, about 32% 220 of the binding sites detected in vivo for five TFs (ESR1, TP53, POU5F1, SOX2, and CTCF) 221 derived from multiple TE families (Bourque et al., 2008). "
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    • "Alu elements are preferentially distributed in gene-rich regions and contain one-third of the total CpG dinucleotides in the human genome (Batzer and Deininger, 2002), as well as many putative transcription factor (TF) binding sites, which may increase their likelihood to either enhance or repress gene expression (Polak and Domany, 2006). Although Alu insertions can mutate functional units, these features have been suggested to reflect a distinct advantageous contribution of Alu elements to the transcriptional landscape of the human genome (Batzer and Deininger, 2002; Cordaux and Batzer, 2009). "
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