The Serum Response Factor and a Putative Novel Transcription Factor Regulate Expression of the Immediate-Early GeneArc/Arg3.1in Neurons
| Autor: | Eric Verdin, Hong Joo Kim, Carol L. Peebles, Steven Finkbeiner, Sean A. Pintchovski |
|---|---|
| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | The Journal of Neuroscience. 29:1525-1537 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | The immediate-early effector geneArc/Arg3.1is robustly upregulated by synaptic activity associated with learning and memory. Here we show in primary cortical neuron culture that diverse stimuli induceArcexpression through new transcription. Searching for regulatory regions important forArctranscription, we found nine DNaseI-sensitive nucleosome-depleted sites at this genomic locus. A reporter gene encompassing these sites responded to synaptic activity in an NMDA receptor–dependent manner, consistent with endogenousArcmRNA. Responsiveness mapped to two enhancer regions ∼6.5 kb and ∼1.4 kb upstream ofArc. We dissected these regions further and found that the proximal enhancer contains a functional and conserved “Zeste-like” response element that binds a putative novel nuclear protein in neurons. Therefore, activity regulatesArctranscription partly by a novel signaling pathway. We also found that the distal enhancer has a functional and highly conserved serum response element. This element binds serum response factor, which is recruited by synaptic activity to regulateArc. Thus,Arcis the first target of serum response factor that functions at synapses to mediate plasticity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|