Dynamic epigenomic landscape of carbon-concentrating mechanisms in the model industrial oleaginous microalga Nannochloropsis oceanica

Despite their ecological and physiological significance, how carbon-concentrating mechanisms (CCM) are regulated in microalgae remains elusive. Here in the model industrial microalga Nannochloropsis oceanica, we uncovered an epigenetic regulatory mechanism for CCM via comprehensive, multi-dimensional epigenomic analyses. Our integrated study reveals the complex interplay among histone modifications, dynamic nucleosome positioning, and 3D chromatin structure in regulating gene expression during low CO2 adaptation, despite minimal DNA methylation. Histone modifications, including lysine acetylation (H3K9ac and H3K27ac), crotonylation (Kcr), and methylation (H3K4me2), were associated with active chromatin states. Significantly altered ChIP-Seq peaks were linked to 43.1% of the differentially expressed genes (DEGs). Notably, H3K4me2 exhibited a distinct dual-peak profile around the transcription start site (TSS), which is unique among microalgae and plants. Chromatin compartment dynamics were correlated with gene expression and histone modifications, particularly H3K4me2, while differentially positioned nucleosomes were associated with key CCM-related genes and transcription factors. To further elucidate the role of H3K4me2, we knocked out its methyltransferase, resulting in genome-wide H3K4me2 peak shifts, slower growth, and reduced photosynthesis. These changes were accompanied by differential expression of key genes of NoHINT and NoPMA2, whose subsequent deletion and overexpression revealed their subtle yet significant impacts on growth and photosynthetic efficiency under low CO2 conditions, with NoHINT regulating growth and NoPMA2 influencing photosynthesis. Finally, we proposed a comprehensive model for epigenetic regulation of CCM in N. oceanica, which established a foundation for enhancing microalgal productivity through targeted epigenetic modifications. HighlightsO_LIMulti-layered epigenetic modifications contribute to the regulation of CCM and its adaptation to low CO2 in N. oceanica. C_LIO_LIThe histone modification H3K4me2 regulates the growth and photosynthesis of N. oceanica under low CO2 conditions. C_LIO_LIH3K4me2 targets NoHINT and NoPMA2 in N. oceanica, with NoHINT influencing growth dynamics and NoPMA2 modulating photosynthetic efficiency under low CO2 conditions. C_LI