Integration of epigenome and lactylome reveals the regulation of lipid production in Nannochloropsis oceanica

Lysine lactylation (Kla) is a kind of novel post-translational modification (PTM), which participates in gene expression and various metabolic processes. Nannochloropsis, a significant oleaginous microalgae of economic significance, demonstrates a remarkable capacity for triacylglycerol (TAG) production under nitrogen stress. To elucidate the involvement of lactylation in lipid synthesis, we conducted ChIP-seq and mRNA-seq analyses to monitor lactylation modifications and transcriptome alterations in Nannochloropsis oceanica. In all, 2,057 genes showed considerable variation between nitrogen deprivation (ND) and nitrogen repletion (NR) conditions, comprising 853 upregulated genes and 1,204 downregulated genes. Moreover, a total of 5,375 differential Kla peaks were identified, including 5,331 gain peaks and 44 loss peaks under ND vs NR. The differential Kla peaks were primarily distributed in the promoter (<= 1 kb) (71.07%), 5’UTR (22.64%), and exon (4.25%). Integrative analysis of ChIP-seq, transcriptome, and previous proteome and lactylome data elucidates the potential mechanism by which lactylation promotes lipid accumulation under ND. Lactylation facilitates autophagy and protein degradation, leading to the recycling of carbon into the tricarboxylic acid (TCA) cycle, thereby providing carbon precursors for lipid synthesis. Additionally, lactylation induces the redirection of carbon from membrane lipids to TAG by upregulating lipases and enhancing the TCA cycle and β-oxidation pathways. This research reveals the regulatory functions of lactylation in lipid metabolism and gene expression in Nannochloropsis, offering a new perspective for the investigation of lipid biosynthesis. Examination of lactylation modifications under nitrogen repletion and nitrogen deprivation in Nannochloropsis oceanica cells.