Genomic profiling of the neuronal target genes of the plasticity-related transcription factor -- Zif268.
The later phases of neuronal plasticity are invariably dependent on gene transcription. Induction of the transcription factor Zif268 (Egr-1) in neurones is closely associated with many forms of functional plasticity, yet the neuronal target genes modulated by Zif268 have not been characterized. After transfection of a neuronal cell line with Zif268 we identified genes that show altered expression using high density microarrays. Although some of the genes identified have previously been associated with forms of neuronal plasticity, the majority have not been linked with neuronal plasticity or Zif268 action. Altered expression of a representative sample of the novel target genes was confirmed in Zif268-transfected PC12 neurones, and in in vitro and in vivo models of Zif268-associated neuronal plasticity. In particular, altered expression of the protease inhibitor Cystatin C and the chemokine Cxcl10 was observed in striatal tissue after haloperidol administration. Surprisingly, the group of identified genes is enriched for components of the proteasome and the major histocompatibility complex. Our findings suggest that altered expression of these genes following Zif268 induction may be a key component of long lasting plasticity in the CNS.
James
Allan B
AB
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, Scotland, UK.
Conway
Ann-Marie
AM
Morris
Brian J
BJ
D000818:Animals; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D020869:Gene Expression Profiling; D023281:Genomics; D017774:Long-Term Potentiation / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements; D014162:Transfection
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat