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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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GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes.

GO::TermFinder comprises a set of object-oriented Perl modules for accessing Gene Ontology (GO) information and evaluating and visualizing the collective annotation of a list of genes to GO terms. It can be used to draw conclusions from microarray and other biological data, calculating the statistical significance of each annotation. GO::TermFinder can be used on any system on which Perl can be run, either as a command line application, in single or batch mode, or as a web-based CGI script. The full source code and documentation for GO::TermFinder are freely available from http://search.cpan.org/dist/GO-TermFinder/.

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
© 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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