Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-sequencing analysis of glucose and acetate regulated transcripts in glioblastoma cells

ABSTRACT: Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. The experiments were performed in quadruplicates for each condition with a total of 12 samples

ORGANISM(S): Homo sapiens

SUBMITTER: Kathryn Wellen

PROVIDER: E-GEOD-57488 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation.

Lee Joyce V JV Carrer Alessandro A Shah Supriya S Snyder Nathaniel W NW Wei Shuanzeng S Venneti Sriram S Worth Andrew J AJ Yuan Zuo-Fei ZF Lim Hee-Woong HW Liu Shichong S Jackson Ellen E Aiello Nicole M NM Haas Naomi B NB Rebbeck Timothy R TR Judkins Alexander A Won Kyoung-Jae KJ Chodosh Lewis A LA Garcia Benjamin A BA Stanger Ben Z BZ Feldman Michael D MD Blair Ian A IA Wellen Kathryn E KE

Cell metabolism 20140703 2

Histone acetylation plays important roles in gene regulation, DNA replication, and the response to DNA damage, and it is frequently deregulated in tumors. We postulated that tumor cell histone acetylation levels are determined in part by changes in acetyl coenzyme A (acetyl-CoA) availability mediated by oncogenic metabolic reprogramming. Here, we demonstrate that acetyl-CoA is dynamically regulated by glucose availability in cancer cells and that the ratio of acetyl-CoA:coenzyme A within the nuc ...[more]

PMID: 24998913

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Project description:Cytosolic acetyl-coenzyme A is a precursor for many biotechnologically relevant compounds produced by Saccharomyces cerevisiae. In this yeast, cytosolic acetyl-CoA synthesis and growth strictly depend on expression of either the Acs1 or Acs2 isoenzyme of acetyl-CoA synthetase (ACS). Since hydrolysis of ATP to AMP and pyrophosphate in the ACS reaction constrains maximum yields of acetyl-CoA-derived products, this study explores replacement of ACS by two ATP-independent pathways for acetyl-CoA synthesis. After evaluating expression of different bacterial genes encoding acetylating acetaldehyde dehydrogenase (A-ALD) and pyruvate-formate lyase (PFL), acs1M-NM-^T acs2M-NM-^T S. cerevisiae strains were constructed in which A-ALD or PFL successfully replaced ACS. In A-ALD-dependent strains, aerobic growth rates of up to 0.27 h-1 were observed, while anaerobic growth rates of PFL-dependent S. cerevisiae (0.21 h-1) were stoichiometrically coupled to formate production. In glucose-limited chemostat cultures, intracellular metabolite analysis did not reveal major differences between A-ALD-dependent and reference strains. However, biomass yields on glucose of A-ALD- and PFL-dependent strains were lower than those of the reference strain. Transcriptome analysis suggested that reduced biomass yields were caused by acetaldehyde and formate in A-ALD- and PFL-dependent strains, respectively. Transcript profiles also indicated that a previously proposed role of Acs2 in histone acetylation is probably linked to cytosolic acetyl-CoA levels rather than to direct involvement of Acs2 in histone acetylation. While, for the first time, demonstrating that yeast ACS can be fully replaced by alternative reactions, this study demonstrates that further modifications are needed to achieve optimal in vivo efficiencies of the supply of acetyl-CoA as product precursor. To investigate the impact of introduced changes in native pathway of cytosolic acetyl-CoA formation in S. cerevisiae, a DNA microarray-based transcriptome analysis was performed on aerobic or anaerobic, glucose-limited chemostat cultures.

Dataset Information

RNA-sequencing analysis of glucose and acetate regulated transcripts in glioblastoma cells

Publications

Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation.

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