Abstract
BackgroundThe 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.ResultsWe 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.ConclusionWe 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.
Highlights
The human genome contains over one million Alu repeat elements whose distribution is not uniform
The Alu consensus sequences are enriched with Binding Motifs We focused on the eight major Alu subfamilies AluJo, Jb, Sx, Sz, Sc, Sq, Sp and Y [3], whose sequences were downloaded from RepBase [29]
In order to find Binding Motif (BM) of a transcription factor (TF), we used its Position Specific Score Matrix (PSSM); 410 Position Specific Score Matrices (PSSMs) were downloaded from two databases [30,31]
Summary
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. BMC Genomics 2006, 7:133 http://www.biomedcentral.com/1471-2164/7/133 which comprise about 10% of the nucleotides of the human genome [1] with over one million inserted copies. This abundance is somewhat of a surprise, since Alu is a non-autonomous retroelement, i.e. it doesn't encode proteins that assist its mobilization, and it needs to rely on the cell's machinery for its duplication in the genome [3]. The major families are: old AluJ, whose members are AluJb and AluJo (both spread in the genome 80–100 mya); the middle, AluS family, which includes AluSx, AluSg, AluSp AluSc and AluSq (35 –50 mya), and the youngest Alu family, AluY (25 mya) [5,6]
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