Effect of Tea Extracts on Metabolic Gene Regulation in Mouse Adipocytes (3T3-L1) and Hepatocytes (AML12)

Nutrient-dependent gene regulation critically contributes to homeostatic control of animal physiology in changing nutrient landscape. In Drosophila, dietary sugars activate transcription factors (TFs), such as Mondo-Mlx, Sugarbabe and Cabut, which control metabolic gene expression to mediate physiological adaptation to high sugar diet. TFs that correspondingly control sugar responsive metabolic genes under conditions of low dietary sugar remain, however, poorly understood. Here we identify a role for Drosophila GATA TF Grain in metabolic gene regulation under both low and high sugar conditions. De novo motif prediction uncovered a significant over-representation of GATA-like motifs on the promoters of sugar-activated genes in Drosophila larvae, which are regulated by Grain, the fly ortholog of GATA1/2/3 subfamily. grain expression is activated by sugar in Mondo-Mlx-dependent manner and it contributes to sugar-responsive gene expression in the fat body. On the other hand, grain displays strong constitutive expression in the anterior midgut, where it drives lipogenic gene expression also under low sugar conditions. Consistently with these differential tissue-specific roles, Grain deficient larvae display delayed development on high sugar diet, while showing deregulated central carbon and lipid metabolism primarily on low sugar diet. Collectively, our study provides evidence for the role of a metazoan GATA transcription factor in nutrient-responsive metabolic gene regulation in vivo.

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Stress-responsive and metabolic gene regulation are altered in low S-adenosylmethionine

10.1101/346205 ◽

2018 ◽

Author(s):

Wei Ding ◽

Daniel P Higgins ◽

Dilip K. Yadav ◽

Read Pukklia-Worley ◽

Amy K Walker

Keyword(s):

Gene Expression ◽

Gene Regulation ◽

Stress Responses ◽

Chromatin Modification ◽

Metabolic Gene ◽

C Elegans ◽

Genome Wide ◽

Heat Shock Responses ◽

Pathogen Response ◽

H3k4 Methyltransferases

AbstractS-adenosylmethionine (SAM) is the methyl donor that modifies proteins such as histones, nucleic acids and produces phosphatidylcholine. Thus variations in SAM levels could affect processes from lipogenesis to epigenetic gene regulation. SAM is hypothesized to link metabolism and chromatin modification, however, its role in acute gene regulation is poorly understood. We recently found that Caenorhabditis elegans with reduced SAM had deficiencies in bacterial-induced H3K4 trimethylation at selected pathogen-response genes, decreasing their expression and limiting survival on the pathogen Pseudomonas aeruginosa. This led us to the hypothesis that SAM may be generally required stress-responsive transcription. Here we show that C. elegans with low SAM fail to activate genome-wide transcriptional programs when exposed to bacterial or xenotoxic stress. However, heat shock responses were unaffected. We also investigated the role of two H3K4 methyltransferases that use SAM, set-2/SET1, and set-16/MLL and found that set-2/SET1 has a specific requirement in bacterial stress responses, whereas set-16/MLL was required for survival in all three stresses. These results define a role for SAM and H3K4 methyltransferases in the acute genome-wide remodeling of gene expression in response to stress. Finally, we find that the ability to modify metabolic gene expression correlates with enhanced survival in stress conditions.

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