Recent studies in yeast reveal an intricate interplay between nuclear envelope (NE) architecture and lipid metabolism, and between lipid signaling and both epigenome and genome integrity. In this review, we highlight the reciprocal connection between lipids and histone modifications, which enable metabolic reprogramming in response to nutrients. The endoplasmic reticulum (ER)-NE regulates the compartmentalization and temporal availability of epigenetic metabolites and its lipid composition also impacts nuclear processes, such as transcriptional silencing and the DNA damage response (DDR). We also discuss recent work providing mechanistic insight into lipid droplet (LD) formation and sterols in the nucleus, and the collective data showing Opi1 as a central factor in both membrane sensing and transcriptional regulation of lipid-chromatin interrelated processes.
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