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Characterization of the mouse adenylyl cyclase type VIII gene promoter: regulation by cAMP and CREB
Author(s) -
Chao Jennifer R.,
Ni Yan G.,
Bolaños Carlos A.,
Rahman Zia,
DiLeone Ralph J.,
Nestler Eric J.
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02186.x
Subject(s) - creb , adenylyl cyclase , creb1 , forskolin , microbiology and biotechnology , biology , transcription factor , promoter , response element , gene expression , gene , genetics , signal transduction , receptor
Adenylyl cyclase (AC) type VIII has been implicated in several forms of neural plasticity, including drug addiction and learning and memory. In the present study, we directly examined the role for the transcription factor CREB (cAMP response element binding protein) in regulating ACVIII expression by cloning a 5.2 kilobase region upstream of the translation start site of the mouse ACVIII gene. Analysis of this fragment revealed consensus elements for several transcription factors, including a canonical cAMP response element (CRE) in close proximity to the transcription initiation region. Next, ACVIII promoter activity was studied in two neural‐derived cell lines and in primary cultures of rat striatal neurons. Activation of the cAMP pathway by forskolin treatment increased promoter activity, and a series of deletion and point mutants demonstrated that this activation is mediated specifically via the canonical CRE site. Gel shift assays confirmed that this site can bind CREB and several CREB family proteins. Further, activation of the ACVIII promoter by forskolin was potentiated by expression of a constitutively active form of CREB, CREB‐VP16, whereas it was inhibited by expression of a dominant‐negative form of CREB, A‐CREB. Finally, over‐expression of CREB in vivo , by viral‐mediated gene transfer, induced ACVIII promoter activity in the brains of ACVIII‐LacZ transgenic mice. These results suggest that the ACVIII gene is regulated by CREB in vitro and in vivo and that this regulation may contribute to CREB‐dependent neural plasticity.