BMC Genomics 2006, 7:133 http://www.biomedcentral.com/1471-2164/7/133 Table 6: Amount of binding motifs (for 25 TFs with Tmax > T1) in the 500 bp and 5000 bp regions of 13686 genes. For each BM we show statistics with respect to sequences that passed Tmax and T5 (see text for further details). We also checked whether the BS resides on Alu or not (see methods). and give the number of BSs that reside on Alu and their percentage out of the total number of BS. 5000 upstream 500 upstream BM name No. of BS on Alu – Tmax %BS on Alu- Tmax No. of BS on Alu T5 %BS on Alu T5 No. of BS on Alu Tmax %BS on Alu Tmax No. of BS on Alu T5 %BS on Alu T5 V$PITX2_Q2 34188 V$LXRE.01 8193 V$GSC.01 33565 V$GFI1.01 32311 V$SREBP.03 7695 V$LYF1.01 26778 V$OTX2.01 35993 V$PAX4.01 9760 V$AARE.01 13854 V$MEF2.04 17253 V$CHREBP_ 1537 MLX_01 V$ER.02 3166 V$NKX25.01 14144 V$LUN1_01 15768 V$HNF4.02 2224 V$MEF2.02 18807 V$RSRFC4.01 18153 V$RSRFC4.02 18424 V$IRF1.01 2116 V$MEF2.03 18027 V$HNF1.03 8819 V$OC2.01 4430 V$RORA1.01 968 V$HNF1.01 2939 V$BRN2.03 2127 99.4% 99.2% 96.0% 95.2% 93.0% 91.8% 84.8% 84.0% 77.3% 76.7% 70.3% 68.2% 67.7% 99.9% 61.5% 56.9% 49.5% 49.0% 48.8% 48.2% 26.9% 25.5% 12.8% 10.3% 6.8% 45546 21686 36033 33557 18264 27476 35993 23265 17047 19766 9810 12256 14754 50303 11368 18807 18153 18424 5343 18027 8819 8643 6891 2939 2127 94.9% 74.9% 90.7% 88.3% 65.9% 84.0% 84.8% 74.7% 62.0% 65.2% 68.6% 50.7% 48.9% 99.6% 61.0% 56.9% 49.5% 49.0% 19.6% 48.2% 26.9% 27.1% 26.7% 10.3% 6.8% 777 185 761 713 181 616 813 207 282 355 49 60 238 340 39 389 381 385 57 383 216 98 25 74 60 99.0% 96.9% 89.2% 84.0% 44.7% 73.5% 64.0% 63.9% 51.1% 58.7% 23.6% 27.6% 32.9% 100.0% 18.9% 30.7% 26.3% 26.7% 20.0% 26.3% 12.9% 15.2% 5.8% 4.5% 4.0% 1022 473 812 742 399 624 813 508 328 414 261 260 249 1143 259 389 381 385 144 383 216 204 152 74 60 86.0% 42.2% 75.5% 68.5% 18.8% 56.1% 64.0% 53.4% 30.5% 43.6% 20.5% 15.9% 18.7% 98.1% 21.6% 30.7% 26.3% 26.7% 7.1% 26.3% 12.9% 16.6% 10.6% 4.5% 4.0% the 66 BMs had more on Alu than off Alu BMs. These BMs include almost all homeodomain proteins, LXRE.01, LYF- 1 and PAX4.01 (but not SIX3, see Fig. 3). In spite of the relatively low Alu density, on-Alu BMs do constitute a sizeable fraction of the putative BMs that are found in the 500 bp long upstream region (Fig. 3 and Table 6). Genes of different biological processes contain different amounts of BSs as a result of differences in their Alu content We used the results of the search for on and off Alu BMs to look for differences between genes that belong to differ- ent biological processes. As expected, for those biological processes whose genes were previously found to be enriched with Alu (Table 6), we also found that a high per- centage of their regulatory signals were on-Alu. The Alu rich groups in this category include metabolic and bio- synthesis associated genes. Since for several TFs a large majority of BMs reside on Alu, we find that Alu-rich func- tional families have a large number of these Alu-associ- ated BMs, whereas Alu-poor biological processes (such as developmental genes) will have less of these BMs (see Fig. 4 and Additional data file 2). For example, the average number of putative BSs of PITX2 is almost 4 times greater in protein biosynthetic genes than in CNS developmental genes (Fig. 4). Interestingly, as a result, developmental TFs such as LYF-1, PAX4, MEF2D and PITX2, that have on-Alu BMs, appear less in the (Alu-poor) upstream region of developmental genes than in the Alu-rich non-develop- mental group of protein biosynthesis related genes. One possible explanation of this may be that the developmen- tal TFs main role is to suppress pathways that are in com- petition with or exclusive of the developmental process (versus acting directly on development – associated genes). One should emphasize that the statements made above are based mainly on in-silico evidence, which must be supplemented by firm experimental observations of bind- ing and functional roles of the bound TFs. Page 8 of 15 (page number not for citation purposes)