SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells.

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PubMed URL:
Linden DJ
Author List: 
Smith-Hicks C
Xiao B
Deng R
Ji Y
Zhao X
Shepherd JD
Posern G
Kuhl D
Huganir RL
Ginty DD
Worley PF
Linden DJ
Nat Neurosci
PubMed ID: 
It has been suggested that gene expression and protein synthesis are required for both long-term memory consolidation and late phases of long-term potentiation and long-term depression (LTD). The necessary genes and the specific transcription factor binding sites in their promoters remain unknown. We found that inhibition of the transcription factor SRF or its cofactor MAL blocked the late phase of LTD in mouse cultured cerebellar Purkinje cells, as did deletion of the immediate early gene Arc. Using neuronal bacterial artificial chromosome (BAC) transfection, we found that, in Arc-/- cells transfected with a wild-type Arc BAC, late-phase LTD was rescued. However, mutation of one SRF-binding site in the Arc promoter (SRE 6.9) blocked this rescue. Co-transfection of wild-type Arc and SRF engineered to bind mutated SRE 6.9 restored late-phase LTD in Arc-/-, SRE 6.9 mutant BAC cells. Thus, SRF binding to SRE 6.9 in the Arc promoter is required for the late phase of cerebellar LTD.
Published Date: 
September, 2010

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