PMID- 22593050 OWN - NLM STAT- MEDLINE DCOM- 20120727 LR - 20211021 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 32 IP - 20 DP - 2012 May 16 TI - Egr-1 induces DARPP-32 expression in striatal medium spiny neurons via a conserved intragenic element. PG - 6808-18 LID - 10.1523/JNEUROSCI.5448-11.2012 [doi] AB - 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. FAU - Keilani, Serene AU - Keilani S AD - Department of Neurology and Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA. FAU - Chandwani, Samira AU - Chandwani S FAU - Dolios, Georgia AU - Dolios G FAU - Bogush, Alexey AU - Bogush A FAU - Beck, Heike AU - Beck H FAU - Hatzopoulos, Antonis K AU - Hatzopoulos AK FAU - Rao, Gadiparthi N AU - Rao GN FAU - Thomas, Elizabeth A AU - Thomas EA FAU - Wang, Rong AU - Wang R FAU - Ehrlich, Michelle E AU - Ehrlich ME LA - eng GR - NS-045942/NS/NINDS NIH HHS/United States GR - R01 HL103575/HL/NHLBI NIH HHS/United States GR - P30 NS061777/NS/NINDS NIH HHS/United States GR - HL103575/HL/NHLBI NIH HHS/United States GR - R01 EY014856/EY/NEI NIH HHS/United States GR - S10 RR022415/RR/NCRR NIH HHS/United States GR - EY014856/EY/NEI NIH HHS/United States GR - R01 NS045942/NS/NINDS NIH HHS/United States GR - R01 HL069908/HL/NHLBI NIH HHS/United States GR - HL069908/HL/NHLBI NIH HHS/United States GR - R01 NS059936/NS/NINDS NIH HHS/United States GR - NS-059936/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32) RN - 0 (Early Growth Response Protein 1) RN - 0 (Nerve Tissue Proteins) RN - 0 (Transcription Factors) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/pharmacology MH - Corpus Striatum/drug effects/*metabolism MH - Dopamine and cAMP-Regulated Phosphoprotein 32/*biosynthesis/*genetics MH - Early Growth Response Protein 1/*metabolism MH - Gene Expression Regulation/drug effects/*genetics MH - Introns/*genetics MH - Mice MH - Nerve Tissue Proteins/metabolism MH - Neurons/metabolism MH - Primary Cell Culture MH - Protein Binding/genetics MH - Rats MH - Sequence Alignment/methods MH - Transcription Factors/*metabolism PMC - PMC3752065 EDAT- 2012/05/18 06:00 MHDA- 2012/07/28 06:00 PMCR- 2012/11/16 CRDT- 2012/05/18 06:00 PHST- 2012/05/18 06:00 [entrez] PHST- 2012/05/18 06:00 [pubmed] PHST- 2012/07/28 06:00 [medline] PHST- 2012/11/16 00:00 [pmc-release] AID - 32/20/6808 [pii] AID - 3773037 [pii] AID - 10.1523/JNEUROSCI.5448-11.2012 [doi] PST - ppublish SO - J Neurosci. 2012 May 16;32(20):6808-18. doi: 10.1523/JNEUROSCI.5448-11.2012.