Similar Datasets
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE228339 | GEO
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE228340 | GEO
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE228335 | GEO
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE228341 | GEO
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE228342 | GEO
Project description:Embryonic cells engage in diverse types of metabolism to execute specialized tasks in the developing embryo. Recent studies have demonstrated that metabolic reprogramming can also drive changes in cell identity and behavior by affecting the expression of developmental genes. However, the connection between cellular metabolism and differential gene expression is still not well understood. Here we report found that histone lactylation, an epigenetic mark derived from glycolysis-derived lactate, couples the metabolic state of embryonic cells with gene expression and the activation of gene regulatory networks. Embryonic tissues with high glycolytic flux, like the neural crest and the pre-somitic mesoderm, display high levels of lactylation. The lactylation mark is dynamically deposited in the loci of neural crest genes as these cells transition to a state of enhanced glycolysis. This process promotes accessibility of active enhancers and is necessary for proper deployment of the neural crest gene regulatory network. When we reduced the deposition of the mark by targeting LDHA and LDHB, lactylated genes were downregulated, and neural crest migration was impeded. Lactylation of neural crest enhancers is controlled by transcription factors SOX9 and YAP/TEAD, which are necessary and sufficient for the deposition of the mark. These findings define an epigenetic mechanism that integrates cellular metabolism with the gene regulatory networks that orchestrate embryonic development.
2023-11-22 | GSE241256 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-02-28 | GSE215268 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-08-21 | GSE168725 | GEO
Project description:The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases1,2. Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer.
| S-EPMC6818755 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-03-01 | GSE251642 | GEO