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 language | English (US) |
|---|---|
| Pages (from-to) | 1082-1089 |
| Number of pages | 8 |
| Journal | Nature Neuroscience |
| Volume | 13 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2010 |
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ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
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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 journal › Article
}
TY - JOUR
T1 - SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells
AU - Smith-Hicks, Constance Leonie
AU - Xiao, Bo
AU - Deng, Rongkang
AU - Ji, Yifei
AU - Zhao, Xia
AU - Shepherd, Jason D.
AU - Posern, Guido
AU - Kuhl, Dietmar
AU - Huganir, Richard L
AU - Ginty, David D.
AU - Worley, Paul F
AU - Linden, David J
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=77956188753&partnerID=8YFLogxK
U2 - 10.1038/nn.2611
DO - 10.1038/nn.2611
M3 - Article
VL - 13
SP - 1082
EP - 1089
JO - Nature Neuroscience
JF - Nature Neuroscience
SN - 1097-6256
IS - 9
ER -