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

Handle URI:
http://hdl.handle.net/10754/552356
Title:
Regional differences in gene expression and promoter usage in aged human brains
Authors:
Pardo, Luba M.; Rizzu, Patrizia; Francescatto, Margherita; Vitezic, Morana; Leday, Gwenaël G.R.; Sanchez, Javier Simon; Khamis, Abdullah M. ( 0000-0002-5945-0159 ) ; Takahashi, Hazuki; van de Berg, Wilma D.J.; Medvedeva, Yulia A.; van de Wiel, Mark A.; Daub, Carsten O.; Carninci, Piero; Heutink, Peter
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.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Regional differences in gene expression and promoter usage in aged human brains 2013, 34 (7):1825 Neurobiology of Aging
Publisher:
Elsevier BV
Journal:
Neurobiology of Aging
Issue Date:
19-Feb-2013
DOI:
10.1016/j.neurobiolaging.2013.01.005
Type:
Article
ISSN:
01974580
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0197458013000237
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorPardo, Luba M.en
dc.contributor.authorRizzu, Patriziaen
dc.contributor.authorFrancescatto, Margheritaen
dc.contributor.authorVitezic, Moranaen
dc.contributor.authorLeday, Gwenaël G.R.en
dc.contributor.authorSanchez, Javier Simonen
dc.contributor.authorKhamis, Abdullah M.en
dc.contributor.authorTakahashi, Hazukien
dc.contributor.authorvan de Berg, Wilma D.J.en
dc.contributor.authorMedvedeva, Yulia A.en
dc.contributor.authorvan de Wiel, Mark A.en
dc.contributor.authorDaub, Carsten O.en
dc.contributor.authorCarninci, Pieroen
dc.contributor.authorHeutink, Peteren
dc.date.accessioned2015-05-06T13:16:59Zen
dc.date.available2015-05-06T13:16:59Zen
dc.date.issued2013-02-19en
dc.identifier.citationRegional differences in gene expression and promoter usage in aged human brains 2013, 34 (7):1825 Neurobiology of Agingen
dc.identifier.issn01974580en
dc.identifier.doi10.1016/j.neurobiolaging.2013.01.005en
dc.identifier.urihttp://hdl.handle.net/10754/552356en
dc.description.abstractTo 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.en
dc.publisherElsevier BVen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0197458013000237en
dc.rightsArchived with thanks to Neurobiology of Aging. http://www.elsevier.com/open-access/userlicense/1.0/en
dc.subjectCAGEen
dc.subjectBrain transcriptomeen
dc.subjectAgingen
dc.titleRegional differences in gene expression and promoter usage in aged human brainsen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalNeurobiology of Agingen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionSection Medical Genomics, Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlandsen
dc.contributor.institutionGABBA Program, Instituto de Ciências Biomédicas Abel Salazar, UP, Porto, Portugalen
dc.contributor.institutionRIKEN Omics Science Center, RIKEN Yokohama Institute, Yokohama, Japanen
dc.contributor.institutionDepartment of Cell and Molecular Biology (CMB), Karolinska Institute, Stockholm, Swedenen
dc.contributor.institutionDepartment of Mathematics, VU University, Amsterdam, The Netherlandsen
kaust.authorMedvedeva, Yuliaen
kaust.authorKhamis, Abdullah M.en
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