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) that participates in gene expression and various
metabolic processes. Nannochloropsis has a remarkable
capacity for triacylglycerol (TAG) production under nitrogen stress.
To elucidate the involvement of lactylation in lipid synthesis, we
conducted chromatin immunoprecipitation sequencing (ChIP-seq) and
mRNA-seq analyses to monitor lactylation modifications and transcriptome
alterations in Nannochloropsis oceanica. In all, 2057 genes showed considerable variation between nitrogen
deprivation (ND) and nitrogen repletion (NR) conditions. Moreover,
a total of 5375 differential Kla peaks were identified, including
5331 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 offers a new perspective
for the investigation of lipid biosynthesis in Nannochloropsis.