BMC Genomics Research article Alu elements contain many binding sites for transcription factors and may play a role in regulation of developmental processes Paz Polak and Eytan Domany* BioMed Central Open Access Address: Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel Email: Paz Polak - paz.polak@weizmann.ac.il; Eytan Domany* - eytan.domany@weizmann.ac.il * Corresponding author Published: 01 June 2006 BMC Genomics 2006, 7:133 doi:10.1186/1471-2164-7-133 This article is available from: http://www.biomedcentral.com/1471-2164/7/133 Received: 23 February 2006 Accepted: 01 June 2006 © 2006 Polak and Domany; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: 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. Results: 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. Conclusion: 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. Background Over 90% of the human and other vertebrate genomes don't have any known functional role [1,2], and as such were considered until recently as "Junk DNA" or genomic "dark matter". A large fraction of the "non-functional" DNA originated from mobile elements [1] such as Alu, Page 1 of 15 (page number not for citation purposes)