title: Computational analysis of reciprocal association of metabolism and epigenetics in the budding yeast: a genome-scale metabolic model (GSMM) approach.
abstract: Metaboloepigenetics is a newly coined term in biological sciences that investigates the crosstalk between epigenetic modifications and metabolism. The reciprocal relation between biochemical transformations and gene expression regulation has been experimentally demonstrated in cancers and metabolic syndromes. In this study, we explored the metabolism-histone modifications crosstalk by topological analysis and constraint-based modeling approaches in the budding yeast. We constructed nine models through the integration of gene expression data of four mutated histone tails into a genome-scale metabolic model of yeast. Accordingly, we defined the centrality indices of the lowly expressed enzymes in the undirected enzyme-centric network of yeast by CytoHubba plug-in in Cytoscape. To determine the global effects of histone modifications on the yeast metabolism, the growth rate and the range of possible flux values of reactions, we used constraint-based modeling approach. Centrality analysis shows that the lowly expressed enzymes could affect and control the yeast metabolic network. Besides, constraint-based modeling results are in a good agreement with the experimental findings, confirming that the mutations in histone tails lead to non-lethal alterations in the yeast, but have diverse effects on the growth rate and reveal the functional redundancy.
authors.affiliation: Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Salehzadeh-Yazdi
authors.affiliation: Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Asgari
authors.affiliation: Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Saboury
authors.affiliation: Laboratory of Systems Biology and Bioinformatics (LBB), Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Masoudi-Nejad
mesh_terms: D044127:Epigenesis, Genetic; D057890:Epigenomics; D015966:Gene Expression Regulation, Fungal; D055106:Genome-Wide Association Study; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D008954:Models, Biological; D004718:Saccharomycetales / Q000235:genetics* / Q000378:metabolism*