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Calcium Regulation of Gene Expression: Insights into the CREB/CRE System in Learning and Memory

This lecture delves into the intricate mechanisms of calcium regulation and its role in gene expression, highlighting the CREB/CRE gene regulation system. Key topics include the phosphorylation of CREB, its interaction with histone acetyltransferases like CBP, and the downstream effects on gene expression linked to fear conditioning and taste aversion. We explore transcriptional targets such as Arc, BDNF, and synaptic tagging mechanisms in long-term potentiation (L-LTP). The session addresses experimental findings, including the impact of various inhibitors and knockout studies on L-LTP, enhancing our understanding of learning and memory mechanisms.

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Calcium Regulation of Gene Expression: Insights into the CREB/CRE System in Learning and Memory

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  1. BIPN 148 Lecture 20

  2. Calcium regulation of gene expression

  3. 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

  4. CREB phosphorylation in fear conditioning

  5. CRE-mediated gene expression in fear conditioning

  6. CREB and taste aversion

  7. CREB and Fear Conditioning

  8. Transcriptional targets of CREB CaMKIV + ERK RSK2 Elk-1 CBP/CREB zif268 CRE SRE C/EBP krox20 Arc AMPAR HOMER BDNF NT-3

  9. 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

  10. 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

  11. 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 

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