Lipids contribute to epigenetic control via chromatin structure and functions

Abstract

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid molecules bound to nucleoproteins of the genome. In vitro, some of these lipids exhibit stoichiometric association with DNA polynucleotides with differential affinities toward certain secondary and tertiary structures. Hydrophobic interactions with inner nuclear membrane could provide attractive anchor points for lipid-modified nucleoproteins in organizing the dynamic genome and accordingly there are precedents for covalent bonds between lipids and core histones and, under certain conditions, even DNA. Advances in biophysics, functional genomics, and proteomics in recent years brought about the first sparks of light that promises to uncover some coherent new level of the epigenetic code governed by certain types of lipid–lipid, DNA–lipid, and protein–lipid interactions among other biochemical lipid transactions in the nucleus. Here, we review some of the older and more recent findings and speculate on how critical nuclear lipid transactions are for individual cells, tissues, and organisms.

One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy

“…According to the growing body of evidences, these metabolic features are common to different types of tumors and are considered now as one of the “hallmarks of cancer” [ 4 , 6 , 169 ]. They provide metabolic plasticity to cancer cells which has an impact on different features such as gene expression [ 170 ], epigenetic control [ 171 ] and drug resistance [ 172 ]. One carbon metabolism provides “building blocks” (nucleotides, certain aminoacids) as well as contributes to epigenetic (SAM for DNA and protein methylation) and redox (glutathione) homeostasis for rapidly proliferating cancer cells.…”

Three-Dimensional Cellular Raman Analysis: Evidence of Highly Ordered Lipids Within Cell Nuclei

“…47 A more mechanistic role was suggested recently when it was demonstrated that lipids can participate in the epigenetic regulation of chromatin function. 48 Of the cells used in these experiments, mitotic MCF-7 cells often displayed irregularly shaped nuclei and ordered lipid regions, more frequently following nocodazole treatment but also following selection using the mitotic shake-off approach. This is not surprising, as MCF-7 cells are reported to have a high degree of mitotic instability, and the irregular shapes of the nuclei and ordered lipid regions likely reflects the irregular distribution of the chromatin with which these lipids are associated.…”

“…47 A more mechanistic role was suggested recently when it was demonstrated that lipids can participate in the epigenetic regulation of chromatin function. 48…”