Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1.
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 >7,000 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.
Lindecke
Antje
A
Institut für Neurobiochemie Universität Witten/Herdecke, Stockumer Strasse 10, D-58448 Witten, Germany.
Korte
Martin
M
Zagrebelsky
Marta
M
Horejschi
Volker
V
Elvers
Margitta
M
Widera
Darius
D
Prüllage
Maria
M
Pfeiffer
Julia
J
Kaltschmidt
Barbara
B
Kaltschmidt
Christian
C
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D017781:Genes, Immediate-Early / Q000235:genetics*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D026362:Serum Response Factor / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D050807:ets-Domain Protein Elk-1 / Q000235:genetics*
D018690:Excitatory Amino Acid Agonists; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012118:Resorcinols; D026362:Serum Response Factor; D050807:ets-Domain Protein Elk-1; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine