title: Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
abstract: 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.
authors.affiliation: Life Science Research Laboratory, Central Research Laboratory, Hitachi, Ltd., Kokubunji, Tokyo, 185-8601, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kimura
authors.forename: Ai
authors.initials: A
authors.lastname: Wakamatsu
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshio
authors.initials: T
authors.lastname: Ota
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Riu
authors.initials: R
authors.lastname: Yamashita
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Yamamoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sekine
authors.forename: Katsuki
authors.initials: K
authors.lastname: Tsuritani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Wakaguri
authors.forename: Shizuko
authors.initials: S
authors.lastname: Ishii
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Kaoru
authors.initials: K
authors.lastname: Saito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Isono
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Irie
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kushida
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yoneyama
authors.forename: Rie
authors.initials: R
authors.lastname: Otsuka
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kanda
authors.forename: Takahide
authors.initials: T
authors.lastname: Yokoi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Masako
authors.initials: M
authors.lastname: Wagatsuma
authors.forename: Katsuji
authors.initials: K
authors.lastname: Murakawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ishida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Asako
authors.initials: A
authors.lastname: Takahashi-Fujii
authors.forename: Tomoo
authors.initials: T
authors.lastname: Tanase
authors.forename: Keiichi
authors.initials: K
authors.lastname: Nagai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakai
authors.forename: Takao
authors.initials: T
authors.lastname: Isogai
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
mesh_terms: D001483:Base Sequence; D018899:CpG Islands / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*