MTHFD1 links folate metabolism to BRD4-mediated transcriptional regulation
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PROVIDER: PRJNA415413 | ENA |
REPOSITORIES: ENA
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Project description:The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for functional regulators and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.
2019-04-04 | GSE105786 | GEO
Project description:The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for genetic and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.
2019-04-04 | PXD012715 | Pride
Project description: Not available
| S-EPMC6952269 | biostudies-literature
Project description:Histone crotonylation links metabolism with gene expression
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Project description:Two maize inbred lines, DAN3130 and JI63, with different patterns of folate accumulation and different total folate contents in mature kernels were used to investigate the transcriptional regulation of folate metabolism during late stages of kernel formation by comparative transcriptome analysis; The fresh kernel samples of each inbred line were collected on DAP 24, DAP 35 days, respectively. Mature kernel samples were harvested after all the plants turned yellow. Three biological replicates of each sample were collected, and total RNA with high quality was pooled and sent for sequencing. Total RNA of high quality was pooled for transcriptome analysis, and raw RNA-seq data of DAP 24, DAP35 and mature kernels for both two inbred lines were obtained. The folate accumulation during DAP 24 to mature kernels could be controlled by circumjacent pathways of folate biosynthesis, such as pyruvate metabolism, glutamate metabolism and serine/glycine metabolism. In addition, the folate variation between these two inbred lines was related to those genes among folate metabolism, such as genes in the pteridine branch, ρ-ABA branch, serine/THF/5-M-THF cycle and the conversion of tetrahydrofolate monoglutamate to tetrahydrofolate polyglutamate; The findings provided insight into folate accumulation mechanisms during maize kernel formation to promote folate biofortification.
2022-04-19 | GSE195815 | GEO
Project description:cea06-02_folate - methotrexate treatment - global analysis of the folate metabolism in Arabidopsis - Treatment of cells of Arabidopsis by methotrexate which is an inhibitor of the synthesis of the folate. Consequently, the pool of folates presents a strong reduction. The goal of this project is to look at the variations of expression in the Arabidopsis genome and specifically in some genes implied in the metabolism of the folate. Keywords: time course,treated vs untreated comparison 10 dye-swap - CATMA arrays
2008-12-18 | E-GEOD-10675 | biostudies-arrayexpress
Project description:cea06-02_folate - methotrexate treatment - global analysis of the folate metabolism in Arabidopsis - Treatment of cells of Arabidopsis by methotrexate which is an inhibitor of the synthesis of the folate. Consequently, the pool of folates presents a strong reduction. The goal of this project is to look at the variations of expression in the Arabidopsis genome and specifically in some genes implied in the metabolism of the folate. Keywords: time course,treated vs untreated comparison
2008-12-19 | GSE10675 | GEO
Project description:Raw MS files for the manuscript, "A novel inhibitor of P. aeruginosa folate metabolism exploits metabolic differences for narrow-spectrum antibiotic targeting", by Chain et al.
2023-12-07 | MSV000093598 | MassIVE
Project description:Folate is important for fetal development and growth, yet its role in placentation is understudied. Here we report that disrupting folate metabolism by the hypomorphic Mtrr mutation in mice causes morphological and functional defects in their placentas that correspond with early- and late-onset fetal growth restriction. Remarkably, Mtrr heterozygous males initiate inheritance of similar placenta phenotypes and fetal growth defects in their wildtype grandprogeny. An integrated genome-wide approach shows placental transcriptional change and epigenetic instability is caused by an intrinsic or ancestral Mtrr mutation, affecting genes important for placenta development and function (e.g., pregnancy specific glycoprotein (Psg)/Ceacams). Crucially, we establish a functional association between mouse placenta transcript levels and fetal size and identify a human PSG gene variant linked to birthweight. This study provides molecular insight into how folate metabolism influences placental development and attributes a potential multigenerational epigenetic mechanism to unexplained cases of fetal growth defects.
2023-06-06 | GSE233481 | GEO
Project description:Defects in homocysteine and folate metabolism are associated with increased risks for neural tube and congenital heart defects, cardiovascular disease and stroke, cancers, and neurodegeneration. In many but not all cases, dietary supplementation with folate significantly reduces the severity and incidence of these conditions. Common polymorphisms modulate these metabolic pathways and disease risks, but do not fully account for the particular birth defects and adult diseases that occur in at-risk individuals. To test whether other pathways contribute to disease pathogenesis, we analyzed global and pathway-specific changes in gene expression and levels of selected metabolites after depletion and repletion of dietary folate in two genetically distinct inbred strains of mice. Compared to the C57BL/6J strain, A/J showed greater homeostatic response to folate perturbation by retaining a higher serum folate level and minimizing global gene expression changes. Remarkably, folate perturbation led to systematic strain-specific differences only in the expression profile of the cholesterol biosynthesis pathway and translated to changes in levels of serum and liver total cholesterol. By genetically increasing serum and liver total cholesterol levels in APOE deficient mice, we modestly but significantly improved folate retention during folate depletion, suggesting an interplay between homocysteine and folate metabolism and cholesterol metabolism. Absence of measurable changes in global methylation patterns or amelioration of effects with supplementation with an alternative methyl donor suggest that dietary folate perturbations do not act through large-scale or general changes in methylation. These results suggest that homeostatic responses in cholesterol metabolism contribute to the beneficial effects of dietary folate supplementation. Keywords: time course, stress response, diet, genetic, homeostasis
2008-08-27 | GSE9242 | GEO