Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness.
We have employed a hidden Markov model (HMM) based on known cAMP responsive elements to search for putative CREB target genes. The best scoring sites were positionally conserved between mouse and human orthologs, suggesting that this parameter can be used to enrich for true CREB targets. Target validation experiments revealed a core promoter requirement for transcriptional induction via CREB; TATA-less promoters were unresponsive to cAMP compared to TATA-containing genes, despite comparable binding of CREB to both sets of genes in vivo. Indeed, insertion of a TATA box motif rescued cAMP responsiveness on a TATA-less promoter. These results illustrate a mechanism by which subsets of target genes for a transcription factor are differentially regulated depending on core promoter configuration.
Conkright
Michael D
MD
Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Guzmán
Ernesto
E
Flechner
Lawrence
L
Su
Andrew I
AI
Hogenesch
John B
JB
Montminy
Marc
M
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D000242:Cyclic AMP / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D019143:Evolution, Molecular; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008390:Markov Chains; D051379:Mice; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016385:TATA Box / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP