Cell-type-specific binding of the transcription factor CREB to the cAMP-response element

Hyunjoo Cha-Molstad, David M. Keller, Gregory S. Yochum, Soren Impey, Richard H. Goodman

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

The cAMP-response element-binding protein (CREB) transcription factor was initially identified as a mediator of cAMP-induced gene expression. CREB binds to a target sequence termed the cAMP-response element (CRE) found in many cellular and viral gene promoters. One of the best-characterized CREs resides in the promoter of the gene encoding the neuropeptide somatostatin, and this element has served as a model for studies of CREB function. Phosphorylation of CREB by protein kinase A allows recruitment of the coactivator CREB-binding protein (CBP). A central tenet of the CREB-CBP model is that CREB binds constitutively to the CRE and that regulation occurs through the phosphorylation-dependent recruitment of CBP. In this report, we use chromatin immunoprecipitation assays to show that CREB does not interact in vivo with the somatostatin CRE, or similar elements in several other genes, in PC12 cells, a standard model for studies of CREB function. Rather, CREB binding in vivo is regulated in a cell-specific manner, a finding that was confirmed by using in vivo genomic footprinting assays. The CREs in other genes were also found to interact differentially with CREB in PC12 cells, hepatoma cells, and cortical neurons. We conclude that the family of CREB target genes differs from one cell type to another and that the ability of CREB to bind to a particular CRE represents an important component of gene regulation.

Original languageEnglish (US)
Pages (from-to)13572-13577
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number37
DOIs
StatePublished - Sep 14 2004

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Cyclic AMP Response Element-Binding Protein
Response Elements
Transcription Factors
Protein Binding
CREB-Binding Protein
PC12 Cells
Somatostatin
Genes
Phosphorylation
Gene Components
Viral Genes
Chromatin Immunoprecipitation
Cyclic AMP-Dependent Protein Kinases
Neuropeptides
Hepatocellular Carcinoma

All Science Journal Classification (ASJC) codes

  • General

Cite this

Cha-Molstad, Hyunjoo ; Keller, David M. ; Yochum, Gregory S. ; Impey, Soren ; Goodman, Richard H. / Cell-type-specific binding of the transcription factor CREB to the cAMP-response element. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 37. pp. 13572-13577.
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Cell-type-specific binding of the transcription factor CREB to the cAMP-response element. / Cha-Molstad, Hyunjoo; Keller, David M.; Yochum, Gregory S.; Impey, Soren; Goodman, Richard H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 37, 14.09.2004, p. 13572-13577.

Research output: Contribution to journalArticle

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