OPERating ON Chromatin, a Colorful Language where Context Matters

Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
Journal of Molecular Biology (Impact Factor: 4.33). 05/2011; 409(1):36-46. DOI: 10.1016/j.jmb.2011.01.040
Source: PubMed

ABSTRACT Histones, the fundamental packaging elements of eukaryotic DNA, are highly decorated with a diverse set of post-translational modifications (PTMs) that are recognized to govern the structure and function of chromatin. Ten years ago, we put forward the histone code hypothesis, which provided a model to explain how single and/or combinatorial PTMs on histones regulate the diverse activities associated with chromatin (e.g., gene transcription). At that time, there was a limited understanding of both the number of PTMs that occur on histones and the proteins that place, remove, and interpret them. Since the conception of this hypothesis, the field has witnessed an unprecedented advance in our understanding of the enzymes that contribute to the establishment of histone PTMs, as well as the diverse effector proteins that bind them. While debate continues as to whether histone PTMs truly constitute a strict "code," it is becoming clear that PTMs on histone proteins function in elaborate combinations to regulate the many activities associated with chromatin. In this special issue, we celebrate the 50th anniversary of the landmark publication of the lac operon with a review that provides a current view of the histone code hypothesis, the lessons we have learned over the last decade, and the technologies that will drive our understanding of histone PTMs forward in the future.

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Available from: Brian D Strahl, Sep 26, 2015
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    • "Consistent with this, studies have shown that both histone mutation and PTM misregulation contribute to the initiation and progression of a wide number of human diseases, including cancer and neurological disorders (Bannister and Kouzarides, 2011; Dawson and Kouzarides, 2012; Funato et al., 2014; Jakovcevski and Akbarian, 2012; Lewis et al., 2013; Rothbart and Strahl, 2014). Histone modifications function in part as docking sites for effector proteins harboring specialized, evolutionarily conserved domains that ''read'' the single or combinatorial modification states of histones (Gardner et al., 2011; Jenuwein and Allis, 2001; Strahl and Allis, 2000). The mass production and distribution of PTM-specific histone antibodies (more than 1,000 are commercially available to date) have greatly facilitated the study of these histone marks and their impact on chromatin function (Perez-Burgos et al., 2004; Turner and Fellows, 1989). "
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    ABSTRACT: Access to high-quality antibodies is a necessity for the study of histones and their posttranslational modifications (PTMs). Here we debut the Histone Antibody Specificity Database (, an online and expanding resource cataloging the behavior of widely used, commercially available histone antibodies by peptide microarray. This interactive web portal provides a critical resource to the biological research community that routinely uses these antibodies as detection reagents for a wide range of applications. Copyright © 2015 Elsevier Inc. All rights reserved.
    Molecular cell 07/2015; 59(3). DOI:10.1016/j.molcel.2015.06.022 · 14.02 Impact Factor
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    • "The basis for the differential expression of HSV genes during lytic infection of epithelial cells versus the expression of only the LAT and miRNAs during latent infection has been an important unanswered question. It has been increasingly recognized that epigenetic mechanisms are central in regulation of eukaryotic gene expression (Gardner et al., 2011), and these regulatory mechanisms also apply to HSV gene expression (Knipe and Cliffe, 2008; Knipe et al., 2013). Herpesviral DNA in the virion is not associated with histones, but instead the negative charges are apparently neutralized by the polyamine spermine. "
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    ABSTRACT: Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. Copyright © 2015 Elsevier Inc. All rights reserved.
    Virology 03/2015; 479-480. DOI:10.1016/j.virol.2015.02.009 · 3.32 Impact Factor
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    • "Through these binding domains, non-histone effectors bind histone modifications, resulting in further chromatin remodeling . Several aspects of the transcriptional process are governed by histone modifications, including enhancer element activation , accessibility of the transcription start site, RNA polymerase recruitment, transcriptional initiation, and others beyond the scope of this review (Weake and Workman, 2010; Gardner et al., 2011). Altered histone modifications have the potential to impact differential gene and subsequent protein expression. "
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    ABSTRACT: Exposure to toxic metals poses a serious human health hazard based on ubiquitous environmental presence, the extent of exposure, and the toxicity and disease states associated with exposure. This global health issue warrants accurate and reliable models derived from the risk assessment process to predict disease risk in populations. There has been considerable interest recently in the impact of environmental toxicants such as toxic metals on the epigenome. Epigenetic modifications are alterations to an individual's genome without a change in the DNA sequence, and include, but are not limited to, three commonly studied alterations: DNA methylation, histone modification, and non-coding RNA expression. Given the role of epigenetic alterations in regulating gene and thus protein expression, there is the potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. In the present review, epigenetic alterations induced by five high priority toxic metals/metalloids are prioritized for analysis and their possible inclusion into the risk assessment process is discussed.
    Frontiers in Genetics 07/2014; 5:201. DOI:10.3389/fgene.2014.00201
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