Histone lactylation couples cellular metabolism with the activation of developmental gene regulatory networks [CUT&RUN control and SOX9/TEA1-VPR over-expressing]
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PROVIDER: PRJNA1007594 | ENA |
REPOSITORIES: ENA
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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.
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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.
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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.
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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.
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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.
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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.
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Project description:Histone lactylation couples cellular metabolism with the activation of developmental gene regulatory networks [SOX9 MO ATAC-seq]
| PRJNA949373 | ENA
Project description:Histone lactylation couples cellular metabolism with the activation of developmental gene regulatory networks [NCC CUT&RUN]
| PRJNA949364 | ENA
Project description:Lysine lactylation (Kla) is a new type of histone mark implicated in the regulation of various functional processes such as transcription. However, how this histone mark acts in cancers remains unexplored due in part to a lack of knowledge about its reader proteins. Here, we observe that cervical cancer (CC) cells undergo metabolic reprogram by which lactate accumulation and thereby boost histone lactylation, particularly H3K14la. Utilizing a multivalent photoaffinity probe in combination with quantitative proteomics approach, we identify DPF2 as a candidate target of H3K14la. Biochemical studies as well as CUT&Tag analysis reveal that DPF2 is capable of binding to H3K14la, and co-localizes with it on promoters of oncogenic genes. Notably, disrupting the association between DPF2 and histone lactylation through structure-guided mutation blunts those cancer-related gene expression along with cell survival. Together, our findings reveal DPF2 as a bona fide H3K14la effector that couples histone lactylation to gene transcription and cell survival, offering insight into how histone Kla engages in transcription and tumorigenesis.
2024-06-17 | GSE267107 | GEO
Project description:Lysine lactylation (Kla) is a new type of histone mark implicated in the regulation of various functional processes such as transcription. However, how this histone mark acts in cancers remains unexplored due in part to a lack of knowledge about its reader proteins. Here, we observe that cervical cancer (CC) cells undergo metabolic reprogram by which lactate accumulation and thereby boost histone lactylation, particularly H3K14la. Utilizing a multivalent photoaffinity probe in combination with quantitative proteomics approach, we identify DPF2 as a candidate target of H3K14la. Biochemical studies as well as CUT&Tag analysis reveal that DPF2 is capable of binding to H3K14la, and co-localizes with it on promoters of oncogenic genes. Notably, disrupting the association between DPF2 and histone lactylation through structure-guided mutation blunts those cancer-related gene expression along with cell survival. Together, our findings reveal DPF2 as a bona fide H3K14la effector that couples histone lactylation to gene transcription and cell survival, offering insight into how histone Kla engages in transcription and tumorigenesis.
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