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Lipids contribute to epigenetic control via chromatin structure and functions

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      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.

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      Global quantification of mammalian gene expression control.

      Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.
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        The language of covalent histone modifications.

        Histone proteins and the nucleosomes they form with DNA are the fundamental building blocks of eukaryotic chromatin. A diverse array of post-translational modifications that often occur on tail domains of these proteins has been well documented. Although the function of these highly conserved modifications has remained elusive, converging biochemical and genetic evidence suggests functions in several chromatin-based processes. We propose that distinct histone modifications, on one or more tails, act sequentially or in combination to form a 'histone code' that is, read by other proteins to bring about distinct downstream events.
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          Membrane lipids: where they are and how they behave.

          Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?
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            Author and article information

            Affiliations
            [1]Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008 and Russian Institute for Advanced Study at Moscow Pedagogical State University, Moscow 119571 Russian Federation
            [2]Wellcome Trust Centre for Cell Biology, University of Edinburgh, Kings Buildings, Michael Swann Bldg., Max Born Crescent, Edinburgh EH9 3BF, UK
            [3]MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK
            [4]Department of Biosciences, P.O. Box 65 (Viikinkaari 1), 00014, University of Helsinki, Helsinki, Finland
            Author notes
            [*]Corresponding author's e-mail address: kagasha@123456yahoo.com
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            Journal
            SOR-LIFE
            ScienceOpen Research
            ScienceOpen
            2199-1006
            06 October 2015
            23 August 2016
            : 0 (ID: 8feb0edb-4724-4f85-9bd4-fd3b0eee2868)
            : 0
            : 1-12
            3754:XE
            10.14293/S2199-1006.1.SOR-LIFE.AUXYTR.v2
            © 2016 Zhdanov et al.

            This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

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            Figures: 2, Tables: 3, References: 87, Pages: 12
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