Sequential increase in Egr-1 and AP-1 DNA binding activity in the dentate gyrus following the induction of long-term potentiation.
Establishment of long-term potentiation (LTP) at perforant path synapses is highly correlated with increased expression of Egr and AP-1 transcription factors in rat dentate gyrus granule cells. We have investigated whether increased transcription factor levels are reflected in increased transcription factor activity by assessing Egr and AP-1 DNA binding activity using gel shift assays. LTP produced an increase in binding to the Egr element, which was NMDA receptor-dependent and correlated closely with our previously reported increase in Egr-1 (zif/268) protein levels. Supershift analysis confirmed involvement of Egr-1, but not Egr-2 in the DNA binding activity. AP-1 DNA binding was also rapidly elevated in parallel with protein levels, however, the peak increase in activity was delayed until 4 h, a time point when we have previously shown that only jun-D protein was elevated. These data indicate that binding of Egr-1 and AP-1 to their response elements is increased in two phases. This may result in activation of distinct banks of target genes which contribute to the establishment of persistent LTP.
Williams
J M
JM
Department of Biochemistry and Centre for Gene Research, University of Otago, Dunedin, New Zealand. joanna.williams@stonebow.otago.ac.nz
Beckmann
A M
AM
Mason-Parker
S E
SE
Abraham
W C
WC
Wilce
P A
PA
Tate
W P
WP
D000818:Animals; D016384:Consensus Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017874:Immediate-Early Proteins; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA