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Journal article
Global mapping of transcription factor motifs in human aging
PloS one, v 13(1), e0190457
02 Jan 2018
PMID: 29293662
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Biological aging is a complex process dependent on the interplay of cell autonomous and tissue contextual changes which occur in response to cumulative molecular stress and manifest through adaptive transcriptional reprogramming. Here we describe a transcription factor (TF) meta-analysis of gene expression datasets accrued from 18 tissue sites collected at different biological ages and from 7 different in-vitro aging models. In-vitro aging platforms included replicative senescence and an energy restriction model in quiescence (ERiQ), in which ATP was transiently reduced. TF motifs in promoter regions of trimmed sets of target genes were scanned using JASPAR and TRANSFAC. TF signatures established a global mapping of agglomerating motifs with distinct clusters when ranked hierarchically. Remarkably, the ERiQ profile was shared with the majority of in-vivo aged tissues. Fitting motifs in a minimalistic protein-protein network allowed to probe for connectivity to distinct stress sensors. The DNA damage sensors ATM and ATR linked to the subnetwork associated with senescence. By contrast, the energy sensors PTEN and AMPK connected to the nodes in the ERiQ subnetwork. These data suggest that metabolic dysfunction may be linked to transcriptional patterns characteristic of many aged tissues and distinct from cumulative DNA damage associated with senescence.
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Details
- Title
- Global mapping of transcription factor motifs in human aging
- Creators
- David J. Alfego (Author) - Drexel UniversityUlrich Rodeck - Thomas Jefferson UniversityAndres Kriete (Author) - Drexel University
- Publication Details
- PloS one, v 13(1), e0190457
- Publisher
- Public LIbrary of Science (PLOS)
- Number of pages
- 16
- Grant note
- This work was funded in part by DOD (UR: WX81XWH-15-1-0618 Department of Defense) and by the Coulter Translational Partnership Program of the School of Biomedical Engineering, Science and Health System (AK). DA was recipient of a GAANN fellowship in bioinformatics.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000419101600124
- Scopus ID
- 2-s2.0-85039840293
- Other Identifier
- 991014632271904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology