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Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE291677 | GEO | 2026/02/26

REPOSITORIES: GEO

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Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_CUT&Tag]

Project description:High aerobic glycolysis in retinal photoreceptors, as in cancer cells, is implicated in mitigating energy and metabolic demands. Lactate, a key product of glycolysis, is implicated in epigenetic regulation through histone lactylation in cancer. Here, we demonstrate that increased ATP production during retinal development is achieved primarily through augmented glycolysis. Histone lactylation, especially H3K18La, parallels enhanced glycolysis and its product, lactate, in developing retina and in retinal explants. Multi-omics analyses, combined with confocal imaging, reveal the localization of H3K18La near H3K27Ac in euchromatin at promoters of active retinal, especially photoreceptor, genes. H3K18La and gene expression also correspond to glucose metabolism in retinal explants. Evaluation of accessible chromatin at H3K18La promoters uncovers an enrichment of GC-rich motifs for transcription factors of SP, KMT and KLF families, among others, indicating specificity of H3K18La-mediated gene regulation. Our results highlight glycolysis/lactate/H3K18La as a regulatory axis in fine-tuning gene expression in developing and mature retina.

2026-03-02 | GSE291663 | GEO

Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_RNA-seq]

2026-03-02 | GSE291661 | GEO

Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [timecourse_CUT&Tag]

2026-03-02 | GSE291664 | GEO

Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_RNA-seq 2]

2026-02-28 | GSE322475 | GEO

Lactate promotes H3K18 lactylation in human neuroectoderm differentiation.

Project description:In mammals, early embryonic gastrulation process is high energy demanding. Previous studies showed that, unlike endoderm and mesoderm cells, neuroectoderm differentiated from human embryonic stem cells relied on aerobic glycolysis as the major energy metabolic process, which generates lactate as the final product. Here we explored the function of intracellular lactate during neuroectoderm differentiation. Our results revealed that the intracellular lactate level was elevated in neuroectoderm and exogenous lactate could further promote hESCs differentiation towards neuroectoderm. Changing intracellular lactate levels by sodium lactate or LDHA inhibitors had no obvious effect on BMP or WNT/β-catenin signaling during neuroectoderm differentiation. Notably, histone lactylation, especially H3K18 lactylation was significant upregulated during this process. We further performed CUT&Tag experiments and the results showed that H3K18la is highly enriched at gene promoter regions. By analyzing data from CUT&Tag and RNA-seq experiments, we further identified that four genes, including PAX6, were transcriptionally upregulated by lactate during neuroectoderm differentiation. A H3K18la modification site at PAX6 promoter was verified and exogenous lactate could also rescue the level of PAX6 after shPAX6 inhibition.

| S-EPMC11576721 | biostudies-literature

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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

2024-02-14 | GSE234027 | GEO

Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina

Project description:Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina

| PRJNA1234637 | ENA

Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

Project description: Not available

| S-EPMC10849771 | biostudies-literature

Histone H3K18 and Ezrin Lactylation Promote Renal Dysfunction in Sepsis-Associated Acute Kidney Injury.

Project description:Histone lactylation is a metabolic stress-related histone modification. However, the role of histone lactylation in the development of sepsis-associated acute kidney injury (SA-AKI) remains unclear. Here, histone H3K18 lactylation (H3K18la) is elevated in SA-AKI, which is reported in this study. Furthermore, this lactate-dependent histone modification is enriched at the promoter of Ras homolog gene family member A (RhoA) and positively correlated with the transcription. Correction of abnormal lactate levels resulted in a reversal of abnormal histone lactylation at the promoter of RhoA. Examination of related mechanism revealed that histone lactylation promoted the RhoA/Rho-associated protein kinase (ROCK) /Ezrin signaling, the activation of nuclear factor-κB (NF-κB), inflammation, cell apoptosis, and aggravated renal dysfunction. In addition, Ezrin can undergo lactylation modification. Multiple lactylation sites are identified in Ezrin and confirmed that lactylation mainly occurred at the K263 site. The role of histone lactylation is revealed in SA-AKI and reportes a novel post-translational modification in Ezrin. Its potential role in regulating inflammatory metabolic adaptation of renal proximal tubule epithelial cells is also elucidated. The results provide novel insights into the epigenetic regulation of the onset of SA-AKI.

| S-EPMC11267308 | biostudies-literature

Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_RNA-seq 2]

Project description:Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_RNA-seq 2]

| PRJNA1429411 | ENA

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