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

Constance Leonie Smith-Hicks, Bo Xiao, Rongkang Deng, Yifei Ji, Xia Zhao, Jason D. Shepherd, Guido Posern, Dietmar Kuhl, Richard L Huganir, David D. Ginty, Paul F Worley, David J Linden

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalNature Neuroscience
Volume13
Issue number9
DOIs
StatePublished - Sep 2010

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Purkinje Cells
Cultured Cells
Bacterial Artificial Chromosomes
Depression
Transfection
Binding Sites
Serum Response Factor
Artificial Cells
Immediate-Early Genes
Long-Term Memory
Long-Term Potentiation
Transcription Factors
Gene Expression
Mutation
Genes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. / Smith-Hicks, Constance Leonie; Xiao, Bo; Deng, Rongkang; Ji, Yifei; Zhao, Xia; Shepherd, Jason D.; Posern, Guido; Kuhl, Dietmar; Huganir, Richard L; Ginty, David D.; Worley, Paul F; Linden, David J.

In: Nature Neuroscience, Vol. 13, No. 9, 09.2010, p. 1082-1089.

Research output: Contribution to journalArticle

Smith-Hicks, Constance Leonie ; Xiao, Bo ; Deng, Rongkang ; Ji, Yifei ; Zhao, Xia ; Shepherd, Jason D. ; Posern, Guido ; Kuhl, Dietmar ; Huganir, Richard L ; Ginty, David D. ; Worley, Paul F ; Linden, David J. / SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. In: Nature Neuroscience. 2010 ; Vol. 13, No. 9. pp. 1082-1089.
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