title: CREB binds to multiple loci on human chromosome 22.
abstract: The cyclic AMP-responsive element-binding protein (CREB) is an important transcription factor that can be activated by hormonal stimulation and regulates neuronal function and development. An unbiased, global analysis of where CREB binds has not been performed. We have mapped for the first time the binding distribution of CREB along an entire human chromosome. Chromatin immunoprecipitation of CREB-associated DNA and subsequent hybridization of the associated DNA to a genomic DNA microarray containing all of the nonrepetitive DNA of human chromosome 22 revealed 215 binding sites corresponding to 192 different loci and 100 annotated potential gene targets. We found binding near or within many genes involved in signal transduction and neuronal function. We also found that only a small fraction of CREB binding sites lay near well-defined 5' ends of genes; the majority of sites were found elsewhere, including introns and unannotated regions. Several of the latter lay near novel unannotated transcriptionally active regions. Few CREB targets were found near full-length cyclic AMP response element sites; the majority contained shorter versions or close matches to this sequence. Several of the CREB targets were altered in their expression by treatment with forskolin; interestingly, both induced and repressed genes were found. Our results provide novel molecular insights into how CREB mediates its functions in humans.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8005, USA>
authors.forename: Ghia
authors.initials: G
authors.lastname: Euskirchen
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Royce
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.forename: Rebecca
authors.initials: R
authors.lastname: Martone
authors.forename: John L
authors.initials: JL
authors.lastname: Rinn
authors.forename: F Kenneth
authors.initials: FK
authors.lastname: Nelson
authors.forename: Fred
authors.initials: F
authors.lastname: Sayward
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.forename: Perry
authors.initials: P
authors.lastname: Miller
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Sherman
authors.initials: S
authors.lastname: Weissman
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000378:metabolism*; D005576:Colforsin / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D011233:Precipitin Tests; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D005576:Colforsin