Exploring the characteristics of sequence elements in proximal promoters of human genes.
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.
Bina
Minou
M
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. Bina@Purdue.edu
Wyss
Phillip
P
Ren
Wenhui
W
Szpankowski
Wojciech
W
Thomas
Elizabeth
E
Randhawa
Ranjit
R
Reddy
Sreedeepti
S
John
Priya M
PM
Pares-Matos
Elsie I
EI
Stein
Arnold
A
Xu
Hao
H
Lazarus
Sheryl A
SA
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*
D020121:5' Untranslated Regions; D014157:Transcription Factors