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Long‐term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk‐1
Author(s) -
Lindecke Antje,
Korte Martin,
Zagrebelsky Marta,
Horejschi Volker,
Elvers Margitta,
Widera Darius,
Prüllage Maria,
Pfeiffer Julia,
Kaltschmidt Barbara,
Kaltschmidt Christian
Publication year - 2006
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 - 10.1111/j.1460-9568.2006.04909.x
Subject(s) - junb , serum response factor , transcription factor , fosb , microbiology and biotechnology , biology , egr1 , immediate early gene , gene expression , response element , gene , promoter , genetics
Long‐term depression (LTD) is one of the paradigms used in vivo or ex vivo for studying memory formation. In order to identify genes with potential relevance for memory formation we used mouse organotypic hippocampal slice cultures in which chemical LTD was induced by applications of 3,5‐dihydroxyphenylglycine (DHPG). The induction of chemical LTD was robust, as monitored electrophysiologically. Gene expression analysis after chemical LTD induction was performed using cDNA microarrays containing >7000 probes. The DHPG‐induced expression of immediate early genes ( c‐fos , junB , egr1 and nr4a1 ) was subsequently verified by TaqMan polymerase chain reaction. Bioinformatic analysis suggested a common regulator element [serum response factor (SRF)/Elk‐1 binding sites] within the promoter region of these genes. Indeed, here we could show a DHPG‐dependent binding of SRF at the SRF response element (SRE) site within the promoter region of c‐fos and junB. However, SRF binding to egr1 promoter sites was constitutive. The phosphorylation of the ternary complex factor Elk‐1 and its localization in the nucleus of hippocampal neurones after DHPG treatment was shown by immunofluorescence using a phosphospecific antibody. We suggest that LTD leads to SRF/Elk‐1‐regulated gene expression of immediate early transcription factors, which could in turn promote a second broader wave of gene expression.