BIPN 148 Lecture 15

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BIPN 148 Lecture 15
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Calcium regulation of gene expression
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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
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CREB phosphorylation in fear conditioning
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CRE-mediated gene expression in fear conditioning
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CREB and taste aversion
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CREB and Fear Conditioning
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Transcriptional targets of CREB
CaMKIV ERK
RSK2
Elk-1
CBP/CREB
zif268
CRE
SRE
C/EBP
krox20
Arc
AMPAR HOMER BDNF NT-3
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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
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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  
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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