Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease

Diego Mastroeni, Elaine Delvaux, Jennifer Nolz, Yuyan Tan, Andrew Grover, Salvatore Oddo, Paul Coleman

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

We have previously reported in Alzheimer's disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD.

Original languageEnglish (US)
Pages (from-to)3121-3129
Number of pages9
JournalNeurobiology of Aging
Volume36
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • Alzheimer's disease
  • Epigenetics
  • H3k4me3
  • Localization

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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