TY - JOUR A1 - Kimura, Kouichi A1 - Wakamatsu, Ai A1 - Suzuki, Yutaka A1 - Ota, Toshio A1 - Nishikawa, Tetsuo A1 - Yamashita, Riu A1 - Yamamoto, Jun-ichi A1 - Sekine, Mitsuo A1 - Tsuritani, Katsuki A1 - Wakaguri, Hiroyuki A1 - Ishii, Shizuko A1 - Sugiyama, Tomoyasu A1 - Saito, Kaoru A1 - Isono, Yuko A1 - Irie, Ryotaro A1 - Kushida, Norihiro A1 - Yoneyama, Takahiro A1 - Otsuka, Rie A1 - Kanda, Katsuhiro A1 - Yokoi, Takahide A1 - Kondo, Hiroshi A1 - Wagatsuma, Masako A1 - Murakawa, Katsuji A1 - Ishida, Shinichi A1 - Ishibashi, Tadashi A1 - Takahashi-Fujii, Asako A1 - Tanase, Tomoo A1 - Nagai, Keiichi A1 - Kikuchi, Hisashi A1 - Nakai, Kenta A1 - Isogai, Takao A1 - Sugano, Sumio T1 - Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes Y1 - 2006/01/01 JF - Genome Research JO - Genome Research SP - 55 EP - 65 DO - 10.1101/gr.4039406 VL - 16 IS - 1 UR - http://genome.cshlp.org/content/16/1/55.abstract N2 - By analyzing 1,780,295 5′-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by more than 500 bp and thus are very likely to constitute mutually distinct alternative promoters. To our surprise, at least 7674 (52%) human RefSeq genes were subject to regulation by putative alternative promoters (PAPs). On average, there were 3.1 PAPs per gene, with the composition of one CpG-island-containing promoter per 2.6 CpG-less promoters. In 17% of the PAP-containing loci, tissue-specific use of the PAPs was observed. The richest tissue sources of the tissue-specific PAPs were testis and brain. It was also intriguing that the PAP-containing promoters were enriched in the genes encoding signal transduction-related proteins and were rarer in the genes encoding extracellular proteins, possibly reflecting the varied functional requirement for and the restricted expression of those categories of genes, respectively. The patterns of the first exons were highly diverse as well. On average, there were 7.7 different splicing types of first exons per locus partly produced by the PAPs, suggesting that a wide variety of transcripts can be achieved by this mechanism. Our findings suggest that use of alternate promoters and consequent alternative use of first exons should play a pivotal role in generating the complexity required for the highly elaborated molecular systems in humans. ER -