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| Status |
Public on Nov 22, 2023 |
| Title |
Histone lactylation couples cellular metabolism with the activation of developmental gene regulatory networks [NCC CUT&RUN] |
| Organism |
Gallus gallus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Examination of the genomic deposition of pan lactylation, h3k18la, h3k27ac, and sox9 in embryonic cell types using CUT&RUN.
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| Contributor(s) |
Merkuri F, Rothstein M, Simoes-Costa M |
| Citation missing |
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| |
| Submission date |
Mar 27, 2023 |
| Last update date |
Nov 23, 2023 |
| Contact name |
Marcos Simoes-Costa |
| Organization name |
Boston Children's Hospital
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| Department |
Pathology
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| Street address |
300 Longwood Ave
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19787 |
Illumina NextSeq 500 (Gallus gallus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE228343 |
Histone lactylation couples cellular metabolism with the activation of developmental gene regulatory networks |
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| Relations |
| BioProject |
PRJNA949364 |
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