title: Predicting promoter activities of primary human DNA sequences.
abstract: We developed a computer program that can predict the intrinsic promoter activities of primary human DNA sequences. We observed promoter activity using a quantitative luciferase assay and generated a prediction model using multiple linear regression. Our program achieved a prediction accuracy correlation coefficient of 0.87 between the predicted and observed promoter activities. We evaluated the prediction accuracy of the program using massive sequencing analysis of transcriptional start sites in vivo. We found that it is still difficult to predict transcript levels in a strictly quantitative manner in vivo; however, it was possible to select active promoters in a given cell from the other silent promoters. Using this program, we analyzed the transcriptional landscape of the entire human genome. We demonstrate that many human genomic regions have potential promoter activity, and the expression of some previously uncharacterized putatively non-protein-coding transcripts can be explained by our prediction model. Furthermore, we found that nucleosomes occasionally formed open chromatin structures with RNA polymerase II recruitment where the program predicted significant promoter activities, although no transcripts were observed.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwashi, Chiba 277-8562, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Irie
authors.forename: Sung-Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Riu
authors.initials: R
authors.lastname: Yamashita
authors.forename: Masahide
authors.initials: M
authors.lastname: Seki
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Yada
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D017930:Genes, Reporter; D015894:Genome, Human; D057809:HEK293 Cells; D006801:Humans; D016014:Linear Models; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D011401:Promoter Regions, Genetic; D012984:Software; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D015533:Transcriptional Activation
chemical_list: D014157:Transcription Factors; D004247:DNA; D008156:Luciferases