The involvement of histone lactylation modification in gestational diabetes mellitus is revealed through ChIP-seq and RNA-seq analyses.

As a novel post-translational modification of proteins, lactylation plays an important role in various aspects of energy metabolism, signal transduction and gene expression. Although the histone lactylation modification has been reported to be involved in glucose metabolism, its role and molecular pathways in gestational diabetes mellitus (GDM) are still unclear. In this study, we analyzed the histone lactylation modification in GDM using RNA-seq and ChIP-seq. Combined with functional analysis, the key genes with differential histone lactylation modification were identified. We found that these differentially modified genes were highly enriched in the AMPK signaling pathway, cAMP signaling pathway and mTOR signaling pathway. By integrating the results of RNA-seq and ChIP-seq analysis, we identified seven up-regulated DEGs (COL6A1, VIPR2, ZMIZ1, PER1, AGPAT2, EPOR and CACNA2D1) with hyper-histone lactylation modification in GDM. Finally, we identified CACNA2D1 as a key gene undergoing differential histone lactylation modification in GDM through ChIP-PCR. In conclusion, this study not only confirmed the involvement of lactate in GDM but also characterized the transcriptomic profile and histone lactylation modification landscape of GDM patients, providing a theoretical basis for the clinical diagnosis and treatment of GDM.