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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

ABSTRACT: Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

PROVIDER: PRJNA979204 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24821167_1.fastq.gz	Fastqsanger.gz
	SRR24821167_2.fastq.gz	Fastqsanger.gz
	SRR24821168_1.fastq.gz	Fastqsanger.gz
	SRR24821168_2.fastq.gz	Fastqsanger.gz
	SRR24821169_1.fastq.gz	Fastqsanger.gz

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [RNA-seq]

Project description:Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [RNA-seq]

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [CUT&TAG]

Project description:Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [CUT&TAG]

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [CUT&TAG]

Project description:Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, and the abnormal phenotypes could be recapitulated by overexpression of H3K18R mutation and rescued by addition of Lac-CoA. By profiling the landscape of H3K18lac in human and mouse preimplantation embryos, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and corelates with their expressions. Taken together, we demonstrate the important role for lactate in major ZGA via H3K18lac, showing a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals [RNA-seq]

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals.

Project description:Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation (ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-CoA and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

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Lactate treatment regulates epigenome of mouse embryonic stem cells (mESCs)

Project description:We treated mESCs with 50mM lactate to examine its impact on mESC epigenome. Interestingly, we found that lactate supplementation stimulated H3K18 lactylation accumulation on a subset of genes, which in turn promoted transcriptional elongation. Our results indicate that lactate supplementation expands transcriptional network of mouse ESCs.

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

Project description:This SuperSeries is composed of the SubSeries listed below.

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Tumor-associated macrophage derived lactate remodeling glioblastoma stem cells immune microenvironment through lactylation in glioblastoma

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