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Publication : Epigenetic induction of EGR-1 expression by the amyloid precursor protein during exposure to novelty.

First Author  Hendrickx A Year  2013
Journal  PLoS One Volume  8
Issue  9 Pages  e74305
PubMed ID  24066134 Mgi Jnum  J:206037
Mgi Id  MGI:5547681 Doi  10.1371/journal.pone.0074305
Citation  Hendrickx A, et al. (2013) Epigenetic induction of EGR-1 expression by the amyloid precursor protein during exposure to novelty. PLoS One 8(9):e74305
abstractText  Following transcriptome comparison of primary cultures isolated from brain of mice expressing or not the amyloid precursor protein APP, we found transcription of the EGR-1 gene to be regulated by APP. In primary cultures of cortical neurons, APP significantly down regulated EGR-1 expression at both mRNA and protein levels in a gamma-secretase independent manner. The intracellular domain of APP did not interact with EGR-1 gene promoter, but enrichment of acetylated histone H4 at the EGR-1 promoter region was measured in APP-/- neurons, as well as in brain of APP-/- mice, in which increase in EGR-1 expression was also measured. These results argue for an important function of APP in the epigenetic regulation of EGR-1 gene transcription both in vitro and in vivo. In APP-/- mice, constitutive overexpression of EGR-1 in brain impaired epigenetic induction of this early transcriptional regulator during exposure to novelty. Altogether, these results indicate an important function of APP in the epigenetic regulation of the transcription of EGR-1, known to be important for memory formation.
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