Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element

Serene Keilani, Samira Chandwani, Georgia Dolios, Alexey Bogush, Heike Beck, Antonis K. Hatzopoulos, Rao Gadiparthi, Elizabeth A. Thomas, Rong Wang, Michelle E. Ehrlich

Research output: Contribution to journalArticle

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Abstract

DARPP-32 (dopamine and adenosine 3′, 5′-cyclic monophosphate cAMP-regulated phosphoprotein, 32 kDa) is a striatal-enriched protein that mediates signaling by dopamine and other first messengers in the medium spiny neurons. The transcriptional mechanisms that regulate striatal DARPP-32 expression remain enigmatic and are a subject of much interest in the efforts to induce a striatal phenotype in stem cells. We report the identification and characterization of a conserved region, also known as H10, in intron IV of the gene that codes for DARPP-32 (Ppp1r1b). This DNA sequence forms multiunit complexes with nuclear proteins from adult and embryonic striata of mice and rats. Purification of proteins from these complexes identified early growth response-1 (Egr-1). The interaction between Egr-1 and H10 was confirmed in vitro and in vivo by super-shift and chromatin immunoprecipitation assays, respectively. Importantly, brain-derived neurotrophic factor (BDNF), aknown inducer of DARPP-32 and Egr-1 expression, enhanced Egr-1 binding to H10 in vitro. Moreover, over expression of Egr-1 in primary striatal neurons induced the expression of DARPP-32, whereas a dominant-negative Egr-1 blocked DARPP-32 induction by BDNF. Together, this study identifies Egr-1 as a transcriptional activator of the Ppp1r1b gene and provides insight into the molecular mechanisms that regulate medium spiny neuron maturation.

Original languageEnglish (US)
Pages (from-to)6808-6818
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number20
DOIs
StatePublished - May 16 2012

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Corpus Striatum
Neurons
Growth
Brain-Derived Neurotrophic Factor
Dopamine
Chromatin Immunoprecipitation
Phosphoproteins
Nuclear Proteins
Adenosine
Introns
Genes
Proteins
Stem Cells
Phenotype

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Keilani, S., Chandwani, S., Dolios, G., Bogush, A., Beck, H., Hatzopoulos, A. K., ... Ehrlich, M. E. (2012). Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element. Journal of Neuroscience, 32(20), 6808-6818. https://doi.org/10.1523/JNEUROSCI.5448-11.2012

Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element. / Keilani, Serene; Chandwani, Samira; Dolios, Georgia; Bogush, Alexey; Beck, Heike; Hatzopoulos, Antonis K.; Gadiparthi, Rao; Thomas, Elizabeth A.; Wang, Rong; Ehrlich, Michelle E.

In: Journal of Neuroscience, Vol. 32, No. 20, 16.05.2012, p. 6808-6818.

Research output: Contribution to journalArticle

Keilani, S, Chandwani, S, Dolios, G, Bogush, A, Beck, H, Hatzopoulos, AK, Gadiparthi, R, Thomas, EA, Wang, R & Ehrlich, ME 2012, 'Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element', Journal of Neuroscience, vol. 32, no. 20, pp. 6808-6818. https://doi.org/10.1523/JNEUROSCI.5448-11.2012
Keilani, Serene ; Chandwani, Samira ; Dolios, Georgia ; Bogush, Alexey ; Beck, Heike ; Hatzopoulos, Antonis K. ; Gadiparthi, Rao ; Thomas, Elizabeth A. ; Wang, Rong ; Ehrlich, Michelle E. / Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 20. pp. 6808-6818.
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AU - Beck, Heike

AU - Hatzopoulos, Antonis K.

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