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

Academic Article
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Overview

authors

  • Keilani, S.
  • Chandwani, S.
  • Dolios, G.
  • Bogush, A.
  • Beck, H.
  • Hatzopoulos, A. K.
  • Rao, G. N.
  • Thomas, Elizabeth
  • Wang, R.
  • Ehrlich, M. E.

publication date

  • May 2012

journal

  • Journal of Neuroscience  Journal

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), a known inducer of DARPP-32 and Egr-1 expression, enhanced Egr-1 binding to H10 in vitro. Moreover, overexpression 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.

subject areas

  • Animals
  • Brain-Derived Neurotrophic Factor
  • Corpus Striatum
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Early Growth Response Protein 1
  • Gene Expression Regulation
  • Introns
  • Mice
  • Nerve Tissue Proteins
  • Neurons
  • Primary Cell Culture
  • Protein Binding
  • Rats
  • Sequence Alignment
  • Transcription Factors
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.5448-11.2012

PubMed ID

  • 22593050
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Additional Document Info

start page

  • 6808

end page

  • 6818

volume

  • 32

issue

  • 20

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