title: Regional differences in gene expression and promoter usage in aged human brains.
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.
authors: Section Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands.
authors: Luba M
authors: LM
authors: Pardo
authors: Patrizia
authors: P
authors: Rizzu
authors: Margherita
authors: M
authors: Francescatto
authors: Morana
authors: M
authors: Vitezic
authors: Gwenaël G R
authors: GG
authors: Leday
authors: Javier Simon
authors: JS
authors: Sanchez
authors: Abdullah
authors: A
authors: Khamis
authors: Hazuki
authors: H
authors: Takahashi
authors: Wilma D J
authors: WD
authors: van de Berg
authors: Yulia A
authors: YA
authors: Medvedeva
authors: Mark A
authors: MA
authors: van de Wiel
authors: Carsten O
authors: CO
authors: Daub
authors: Piero
authors: P
authors: Carninci
authors: Peter
authors: P
authors: Heutink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000473:pathology* / Q000502:physiology*; D002421:Caudate Nucleus / Q000473:pathology / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011699:Putamen / Q000473:pathology / Q000502:physiology; D013702:Temporal Lobe / Q000473:pathology / Q000502:physiology