Lipids contribute to epigenetic control via chromatin structure and functions: Epigenetics is Getting Fat: How lipids may be involved in the structure of the genome and it's regulation

Abstract

Isolated cases of experimental evidence over the last few decades have shown that, where specifically tested, both prokaryotes and eukaryotes have specific lipid species bound to nucleoproteins of the genome. In vitro, some of these lipid species 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 DNA-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. INTRODUCTION The importance of many lipid classes in biology is without question as they act as secondary messengers and signaling molecules that are added post-translationally to proteins to regulate their function and targeting. Species of a variety of lipid classes (e.g., phospholipids, sphingolipids, neutral lipids, cholesterol, fatty acids) are also responsible for the formation of membrane barriers between cellular compartments. Membrane lipids hold a unique place among cellular biomolecules for their dual nature: they have both hydrophobic long carbon side chains (up to 28 carbon atoms chain length, presumably of trans-configuration and rarely hydroxylated) and hydrophilic polar head groups (conjugated to hydrophobic part by esterand/or ether bond) that enable them to interact with both organic and aqueous environments. To form lipid bilayer membranes, the hydrophobic regions interact with one another while their polar side chains on the outside interact with the aqueous cellular environment. At the same time, a variety of lipid classes at the edge of the cellular compartment provide a stably organized hydrophobic environment to support functions SOR-LIFE