English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

We previously demonstrated that APP epigenetically regulates  Egr1  expression both in cultured neurons and  in vivo . Since  Egr1  is an immediate early gene involved in memory formation, we wondered whether other early genes involved in memory were regulated by APP and we studied molecular mechanisms involved. By comparing prefrontal (PF) cortex from wild type (APP+/+) and APP knockout mice (APP−/−), we observed that APP down regulates expression of four immediate early genes,  Egr1 ,  c-Fos ,  Bdnf  and  Arc . Down regulation of  Egr1 ,  c-Fos  and  Bdnf  transcription resulted from a decreased enrichment of acetylated histone H4 on the corresponding gene promoter. Further characterization of H4 acetylation at  Egr1  and  c-Fos  promoters revealed increased acetylation of H4K5 and H4K12 residues in APP−/− mice. Whereas APP affected  Egr1  promoter activity by reducing access of the CREB transcription factor, its effect on  c-Fos  appeared to depend on increased recruitment of HDAC2 histone deacetylase to the gene promoter. The physiological relevance of the epigenetic regulation of  Egr1  and  c-Fos  gene transcription by APP was further analyzed following exposure of mice to novelty. Although transcription of  Egr1  and  c-Fos  was increased following exposure of APP+/+ mice to novelty, such an induction was not possible in APP−/− mice with a high basal level of expression of these immediate early genes. Altogether, these results demonstrate that APP-mediated regulation of  c-Fos  and  Egr1  by different epigenetic mechanisms is needed for their induction during exposure to novelty.

Epigenetic Regulations of Immediate Early Genes Expression Involved in Memory Formation by the Amyloid Precursor Protein of Alzheimer Disease