Regional differences in gene expression and promoter usage in aged human brains

Luba M. Pardo, Patrizia Rizzu, Margherita Francescatto, Morana Vitezic, Gwenaël G.R. Leday, Javier Simon Sanchez, Abdullah M. Khamis, Hazuki Takahashi, Wilma D.J. van de Berg, Yulia Medvedeva, Mark A. van de Wiel, Carsten O. Daub, Piero Carninci, Peter Heutink

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.
Original languageEnglish (US)
Pages (from-to)1825-1836
Number of pages12
JournalNeurobiology of Aging
Volume34
Issue number7
DOIs
StatePublished - Feb 19 2013

ASJC Scopus subject areas

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

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