title: Exploring the characteristics of sequence elements in proximal promoters of human genes.
abstract: Central to reconstruction of cis-regulatory networks is identification and classification of naturally occurring transcription factor-binding sites according to the genes that they control. We have examined salient characteristics of 9-mers that occur in various orders and combinations in the proximal promoters of human genes. In evaluations of a dataset derived with respect to experimentally defined transcription initiation sites, in some cases we observed a clear correspondence of highly ranked 9-mers with protein-binding sites in genomic DNA. Evaluations of the larger dataset, derived with respect to the 5' end of human ESTs, revealed that a subset of the highly ranked 9-mers corresponded to sites for several known transcription factor families (including CREB, ETS, EGR-1, SP1, KLF, MAZ, HIF-1, and STATs) that play important roles in the regulation of vertebrate genes. We identified several highly ranked CpG-containing 9-mers, defining sites for interactions with the CREB and ETS families of proteins, and identified potential target genes for these proteins. The results of the studies imply that the CpG-containing transcription factor-binding sites regulate the expression of genes with important roles in pathways leading to cell-type-specific gene expression and pathways controlled by the complex networks of signaling systems.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. Bina@Purdue.edu
authors.forename: Minou
authors.initials: M
authors.lastname: Bina
authors.forename: Phillip
authors.initials: P
authors.lastname: Wyss
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ren
authors.forename: Wojciech
authors.initials: W
authors.lastname: Szpankowski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thomas
authors.forename: Ranjit
authors.initials: R
authors.lastname: Randhawa
authors.forename: Sreedeepti
authors.initials: S
authors.lastname: Reddy
authors.forename: Priya M
authors.initials: PM
authors.lastname: John
authors.forename: Elsie I
authors.initials: EI
authors.lastname: Pares-Matos
authors.forename: Arnold
authors.initials: A
authors.lastname: Stein
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Lazarus
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D019295:Computational Biology; D030541:Databases, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020218:Response Elements / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D014157:Transcription Factors