p-S133 CREB1, MEF2D and SRF bind the ARC gene

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Homo sapiens
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Activity-responsive transcription of the ARC gene is driven in part by a Synaptic Activity Response Element located ~7kb upstream of the transcription start site. This element is bound by CREB, SRF and MEF2D as assessed by EMSA and ChIP in mouse cells (Kawashima et al, 2009). SARE-driven ARC expression is responsive to stimulation through AMPAR and NMDAR activity, and depends on CaMK and MAPK signaling pathways, consistent with previous studies (Kawashima et al, 2009; Falvell et al, 2006; Ramanan et al, 2005; Bourtchuladze et al, 1994; reviewed in Inoue et al, 2010; Finkbeiner et al, 1997; Epstein and Finkbeiner, 2018). Additional binding sites for SRF, MEF2D and ELK1 were also identified in another study, along with putative binding sites for an as-yet uncharacterized Zeste-like mammalian homologue (Pintchovski et al, 2006).

Literature References
PubMed ID Title Journal Year
29559111 The Arc of cognition: Signaling cascades regulating Arc and implications for cognitive function and disease

Epstein, I, Finkbeiner, S

Semin. Cell Dev. Biol. 2018
19193899 The serum response factor and a putative novel transcription factor regulate expression of the immediate-early gene Arc/Arg3.1 in neurons

Verdin, E, Peebles, CL, Finkbeiner, S, Kim, HJ, Pintchovski, SA

J. Neurosci. 2009
15880109 SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability

Linden, DJ, Ramanan, N, Schütz, G, Sarsfield, S, Ginty, DD, Lemberger, T, Shen, Y

Nat. Neurosci. 2005
7923378 Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein

Schütz, G, Bourtchuladze, R, Blendy, J, Frenguelli, B, Silva, AJ, Cioffi, D

Cell 1994
19116276 Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons

Takemoto-Kimura, S, Kawashima, T, Okamura, M, Worley, PF, Kyo, N, Bito, H, Okuno, H, Nonaka, M, Adachi-Morishima, A

Proc. Natl. Acad. Sci. U.S.A. 2009
16484497 Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number

Greenberg, ME, Kim, TK, Griffith, EC, Paradis, S, Hu, LS, Lin, Y, Cowan, CW, Greer, PL, Chen, C, Flavell, SW

Science 2006
9390517 CREB: a major mediator of neuronal neurotrophin responses

Greenberg, ME, Tavazoie, SF, Finkbeiner, S, Harris, KM, Jacobs, KM, Maloratsky, A

Neuron 1997
21057636 Synaptic activity-responsive element (SARE): A unique genomic structure with an unusual sensitivity to neuronal activity

Kawashima, T, Bito, H, Yagishita-Kyo, N, Okuno, H, Nonaka, M, Inoue, M

Commun Integr Biol 2010
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