Aerobic glycolysis and lactate regulate histone H3K18Lactylation occupancy to fine-tune gene expression in developing and mature retina

Gaur, Mohita, Liang, Xulong, Brooks, Matthew J, Jiang, Ke, Kumari, Anjani, English, Milton A, Cifani, Paolo, Panepinto, Maria C, Nellissery, Jacob, Fariss, Robert N, Campello, Laura, Marchal, Claire, Swaroop, Anand (April 2025) Aerobic glycolysis and lactate regulate histone H3K18Lactylation occupancy to fine-tune gene expression in developing and mature retina. bioRxiv. ISSN 2692-8205 (Submitted)

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Abstract

High aerobic glycolysis in retinal photoreceptors, as in cancer cells, is implicated in mitigating energy and metabolic demands. Lactate, a product of glycolysis, plays a key role 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 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 genes. H3K18La and gene expression are also concordant with glucose metabolism in retinal explants. Evaluation of accessible chromatin at H3K18La marked 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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > tissues types and functions > retina
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Cifani lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 20 April 2025
Date Deposited: 15 Aug 2025 18:28
Last Modified: 15 Aug 2025 18:28
PMCID: PMC12190749
Related URLs:
URI: https://repository.cshl.edu/id/eprint/41939

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