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, Aug 14, 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; DOI:10.1016/j.molcel.2015.06.022 · 14.46 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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    • "DNA is compacted in chromosomes within units called nucleosomes . Approximately 147 base pairs of DNA are wrapped around each nucleosome (Gardner et al., 2011). Each nucleosome is comprised of an octamer of four histone (H) proteins, two each of H2A, H2B, H3, and H4, all of which have an N-terminal tail that can be altered by post-translational modifications (PTMs) including acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation (Fig. 1) (Eickbush and Moudrianakis, 1978; Rothbart and Strahl, 2014). "
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    ABSTRACT: Hippocampal memory formation is highly regulated by post-translational histone modifications and DNA methylation. Accordingly, these epigenetic processes play a major role in the effects of modulatory factors, such as sex steroid hormones, on hippocampal memory. Our laboratory recently demonstrated that the ability of the potent estrogen 17β-estradiol (E2) to enhance hippocampal-dependent novel object recognition memory in ovariectomized female mice requires ERK-dependent histone H3 acetylation and DNA methylation in the dorsal hippocampus. Although these data provide valuable insight into the chromatin modifications that mediate the memory-enhancing effects of E2, epigenetic regulation of gene expression is enormously complex. Therefore, more research is needed to fully understand how E2 and other hormones employ epigenetic alterations to shape behavior. This review discusses the epigenetic alterations shown thus far to regulate hippocampal memory, briefly reviews the effects of E2 on hippocampal function, and describes in detail our work on epigenetic regulation of estrogenic memory enhancement.
    Frontiers in Neuroendocrinology 05/2014; 35(4). DOI:10.1016/j.yfrne.2014.05.001 · 7.58 Impact Factor
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