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CREB has a context‐dependent role in activity‐regulated transcription and maintains neuronal cholesterol homeostasis
Author(s) -
Lemberger Thomas,
Parkitna Jan Rodriguez,
Chai Minqiang,
Schütz Günther,
Engblom David
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-107888
Subject(s) - creb , transcription factor , biology , cyclic amp response element binding protein , microbiology and biotechnology , forebrain , response element , regulation of gene expression , gene expression , gene knockdown , transcription (linguistics) , gene , neuroscience , genetics , promoter , central nervous system , linguistics , philosophy
Induction of specific gene expression patterns in response to activity confers functional plasticity to neurons. A principal role in the regulation of these processes has been ascribed to the cAMP responsive element binding protein (CREB). Using genomewide expression profiling in mice lacking CREB in the forebrain, accompanied by deletion of the cAMP responsive element modulator gene (CREM), we here show that the role of these proteins in activity‐induced gene expression is surprisingly selective and highly context dependent. Thus, only a very restricted subset of activity‐induced genes ( i.e., Gadd45b or Nr4a2 ) requires these proteins for their induction in the hippocampus after kainic acid administration, while they are required for most of the cocaine‐induced expression changes in the striatum. Interestingly, in the absence of CREB, CREM is able to rescue activity‐regulated transcription, which strengthens the notion of overlapping functions of the two proteins. In addition, we show that cholesterol metabolism is dysregulated in the brains of mutant mice, as reflected coordinated expression changes in genes involved in cholesterol synthesis and neuronal accumulation of cholesterol. These findings provide novel insights into the role of CREB and CREM in stimulus‐dependent transcription and neuronal homeostasis.—Lemberger, T., Parkitna, J. R., Chai, M., Schütz, G., Engblom, D. CREB has a context‐dependent role in activity‐regulated transcription and maintains neuronal cholesterol homeostasis FASEB J. 22, 2872–2879 (2008)