BMC Genomics 2006, 7:133 http://www.biomedcentral.com/1471-2164/7/133 Table 5: List of biological processes and statistics of the corresponding Alu content in the 5 kbp upstream regions of the associated genes. Biological process number of genes number of Alu Average number per gene Ttest p-value central nervous system development skeletal development potassium ion transport organogenesis cell-cell adhesion neurogenesis cell-cell signaling morphogenesis cell adhesion muscle development sensory perception ion transport inflammatory response development immune response response to external stimulus cell communication signal transduction genome metabolism cell cycle biosynthesis intracellular transport protein localization protein biosynthesis mrna processing rna processing rna splicing rna metabolism ribosome biogenesis translation 86 105 128 816 114 335 470 1010 471 150 234 573 181 1519 635 910 2535 2017 13686 5605 651 899 406 418 452 205 322 173 391 43 138 167 210 270 1986 281 835 1190 2606 1288 412 646 1595 507 4274 1853 2727 7885 6538 49748 21936 2751 3827 1840 1981 2155 1006 1611 872 1987 223 743 1.94 2.00 2.11 2.43 2.46 2.49 2.53 2.58 2.74 2.74 2.76 2.78 2.80 2.81 2.92 3.00 3.11 3.24 3.63 3.91 4.23 4.26 4.53 4.74 4.77 4.91 5.00 5.04 5.08 5.19 5.39 1.73E-06 2.13E-07 9.41E-08 4.63E-25 1.28E-04 2.20E-10 3.18E-13 9.42E-24 2.54E-09 7.95E-04 3.76E-05 5.06E-10 5.50E-04 3.92E-21 4.21E-08 7.05E-09 3.66E-14 2.79E-07 1 6.85E-08 5.56E-06 2.92E-08 3.86E-08 7.15E-12 3.24E-13 2.37E-08 6.70E-14 1.42E-08 3.66E-18 1.62E-03 2.62E-10 We found that for 29 BMs out of the 66 the majority of putative BSs that pass Tmax reside on Alu sequences; the relative on and off Alu BM content is presented, for 19 out of these 66, in Fig 2. For example, for 5 out the 6 nuclear factors (Table 4) whose BMs appear among the 66, between 66% and 99% of the BMs (found in the 5000 bp upstream regions) are on Alu (see Fig. 2). The highest over-representations in Alu were observed for the BS of PITX2; over 99% of the 34000 BSs that pass the threshold were on Alu, and for LXRE's BSs over 99% of it's 9000 BSs that pass the threshold were on Alu, (see Fig. 2). In gen- eral, the distributions of putative BSs of TFs that bind to TGTAATCCC (Table 1) exhibit remarkable differences between the number of putative BS on and off Alu; over 90% of the total number of putative BSs of these TFs are located within Alu sequences. More moderate differences were found for developmental TFs such as SIX3.01, PAX4.01, NRL.01, MEF2.04 and NKX25.01 (Fig. 2). In general, for every BM that passed FDR of Q = 0.2 (see Table 1) over 80% of the BSs on the 5 kbp upstream region are located on Alu. On the other hand, for the 37 (out of 66) remaining PSSMs the majority of BSs were not located on Alu, like IRF1.01 (48% out of the total number of 4000 BS were located on Alu) and HNF1.03 (27%). Still, even for these TFs, with mainly off-Alu BMs, the Alu repeats provide between hundreds to thousands of putative BSs in the 5 kbp upstream regions (see Table 6). As mentioned above, in the 500 bp upstream region, which constitutes the proximal promoter [46] and hence is believed to be most important for regulation, the Alu density is below the genome average (Fig. 1). To study this region in more detail, we repeated the analysis that was done for the 5000 bp region, and compared the distribu- tions of BSs on and off Alu in the first 500 bp upstream to the TSS (see Fig 3 for 19 representative TFs). Only 9 out of Page 7 of 15 (page number not for citation purposes)