Article (Scientific journals)
Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network
GALHARDO, Mafalda Sofia; SINKKONEN, Lasse; Berninger, Philippe et al.
2013In Nucleic Acids Research
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Abstract :
[en] Metabolic diseases and comorbidities represent an ever-growing epidemic where multiple cell types impact tissue homeostasis. Here, the link between the metabolic and gene regulatory networks was studied through experimental and computational analysis. Integrating gene regulation data with a human metabolic network prompted the establishment of an open-sourced web portal, IDARE (Integrated Data Nodes of Regulation), for visualizing various gene-related data in context of metabolic pathways. Motivated by increasing availability of deep sequencing studies, we obtained ChIP-seq data from widely studied human umbilical vein endothelial cells. Interestingly, we found that association of metabolic genes with multiple transcription factors (TFs) enriched disease-associated genes. To demonstrate further extensions enabled by examining these networks together, constraintbased modeling was applied to data from human preadipocyte differentiation. In parallel, data on gene expression, genome-wide ChIP-seq profiles for peroxisome proliferator-activated receptor (PPAR) c, CCAAT/enhancer binding protein (CEBP) a, liver X receptor (LXR) and H3K4me3 and microRNA target identification for miR-27a, miR-29a and miR-222 were collected. Disease-relevant key nodes, including mitochondrial glycerol-phosphateacyltransferase (GPAM), were exposed from metabolic pathways predicted to change activity by focusing on association with multiple regulators. In both cell types, our analysis reveals the convergence of microRNAs and TFs within the branched chain amino acid (BCAA) metabolic pathway, possibly providing an explanation for its downregulation in obese and diabetic conditions.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
GALHARDO, Mafalda Sofia  ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
SINKKONEN, Lasse   ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Berninger, Philippe;  University of Basel > Biozentrum
LIN, Jake ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
SAUTER, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
HEINÄNIEMI, Merja ;  University of Eastern Finland > A. I. Virtanen Institute for Molecular Sciences
 These authors have contributed equally to this work.
External co-authors :
yes
Language :
English
Title :
Integrated analysis of transcript-level regulation of metabolism reveals disease-relevant nodes of the human metabolic network
Publication date :
05 November 2013
Journal title :
Nucleic Acids Research
ISSN :
1362-4962
Publisher :
Oxford University Press, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
University of Luxembourg - UL
Available on ORBilu :
since 19 November 2013

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