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BIPN 148 Lecture 15. Calcium regulation of gene expression. PO 4. PO 4. The CREB/CRE Gene Regulation System. acetylation. pKAF. Histone. CREB Binding Protein (CBP). RNA Helicase A. ser 133. ser 133. RNA Polymerase II. Basal Transcription Factor IID (TFIID) Complex. CREB. CREB.
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PO4 PO4 The CREB/CRE Gene Regulation System acetylation pKAF Histone CREB Binding Protein (CBP) RNA Helicase A ser 133 ser 133 RNA Polymerase II Basal Transcription Factor IID (TFIID) Complex CREB CREB Target Gene cAMP Response Element 5’-TGACGTCA-3’ TATA Sequence
Transcriptional targets of CREB CaMKIV + ERK RSK2 Elk-1 CBP/CREB zif268 CRE SRE C/EBP krox20 Arc AMPAR HOMER BDNF NT-3
Synaptic Tagging and LTP New gene products or proteins New gene products or proteins Synaptic tag NMDAR Signal to nucleus Synaptic Potentiation Locally generated tag captures new gene product
THE CASE FOR GENE EXPRESSION IN L-LTP EXPERIMENT TYPE and FINDING Block Block of L-LTP with protein/RNA synthesis inhibitors Block of L-LTP with RNA synthesis inhibitors Loss of L-LTP with CREB KOs Block of L-LTP with Arc antisense Loss of L-LTP with CaMKIV KO Loss of L-LTP with zif268 KO
THE CASE FOR GENE EXPRESSION IN L-LTP EXPERIMENT TYPE and FINDING Measure Increased zif268/krox24 mRNA Increased krox20 Increased expression of fos, jun IEG mRNAs Increased CREB phosphorylation Increased CRE read-out Increased elk-1 phosphorylation Increased Arc/Arg3.1 mRNA expression Increased AMPA receptor protein Increased BDNF message