Nucleosome Structure(s) and Stability: Variations on a Theme

Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
Annual Review of Biophysics (Impact Factor: 15.44). 07/2010; 40(1):99-117. DOI: 10.1146/annurev-biophys-042910-155329
Source: PubMed


Chromatin is a highly regulated, modular nucleoprotein complex that is central to many processes in eukaryotes. The organization of DNA into nucleosomes and higher-order structures has profound implications for DNA accessibility. Alternative structural states of the nucleosome, and the thermodynamic parameters governing its assembly and disassembly, need to be considered in order to understand how access to nucleosomal DNA is regulated. In this review, we provide a brief historical account of how the overriding perception regarding aspects of nucleosome structure has changed over the past thirty years. We discuss recent technical advances regarding nucleosome structure and its physical characterization and review the evidence for alternative nucleosome conformations and their implications for nucleosome and chromatin dynamics.

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    • "The fundamental unit for genome compaction in eukaryotic cells is the nucleosome, in which $147 base pairs of DNA wrap $1.7 turns around a histone octamer core (Kornberg, 1974). Nucleosome dynamics regulates replication, repair, and transcription (Andrews and Luger, 2011; Bintu et al., 2012; Kulaeva et al., 2013; Li et al., 2007; Nag and Smerdon, 2009). Nucleosomal DNA can be invaded either passively due to spontaneous fluctuations (Hodges et al., 2009; Koopmans et al., 2007; Li et al., 2005; Li and Widom, 2004) or actively by forces generated by polymerases and chromatin remodelers (Sirinakis et al., 2011; Yin et al., 1995). "
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    ABSTRACT: Dynamics of the nucleosome and exposure of nucleosomal DNA play key roles in many nuclear processes, but local dynamics of the nucleosome and its modulation by DNA sequence are poorly understood. Using single-molecule assays, we observed that the nucleosome can unwrap asymmetrically and directionally under force. The relative DNA flexibility of the inner quarters of nucleosomal DNA controls the unwrapping direction such that the nucleosome unwraps from the stiffer side. If the DNA flexibility is similar on two sides, it stochastically unwraps from either side. The two ends of the nucleosome are orchestrated such that the opening of one end helps to stabilize the other end, providing a mechanism to amplify even small differences in flexibility to a large asymmetry in nucleosome stability. Our discovery of DNA flexibility as a critical factor for nucleosome dynamics and mechanical stability suggests a novel mechanism of gene regulation by DNA sequence and modifications. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 03/2015; 160(6):1135-1144. DOI:10.1016/j.cell.2015.02.001 · 32.24 Impact Factor
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    • "One mechanism includes changing the chemical composition of DNA by the addition of a methyl group that is usually associated with transcriptional repression (Fig. 1) (Smith and Meissner 2013). DNA is wrapped around eight histone proteins to form nucleosomes (Fig. 2A), and a second mechanism involves modifying specific amino acid residues on the histone tails (Fig. 2B) (Andrews and Luger 2011). These posttranslational histone modifications are able to recruit additional proteins that either positively or negatively affect transcription (Fig. 2C) (Barski et al. 2007; Wang et al. 2008). "
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    ABSTRACT: In a cell, the chromatin state is controlled by the highly regulated interplay of epigenetic mechanisms ranging from DNA methylation and incorporation of different histone variants to posttranslational modification of histones and ATP-dependent chromatin remodeling. These changes alter the structure of the chromatin to either facilitate or restrict the access of transcription machinery to DNA. These epigenetic modifications function to exquisitely orchestrate the expression of different genes, and together constitute the epigenome of a cell. In the skin, different epigenetic regulators form a regulatory network that operates to guarantee skin stem cell maintenance while controlling differentiation to multiple skin structures. In this review, we will discuss recent findings on epigenetic mechanisms of skin control and their relationship to skin pathologies.
    Cold Spring Harbor Perspectives in Medicine 02/2014; 4(2). DOI:10.1101/cshperspect.a015263 · 9.47 Impact Factor
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    • "If there are real differences in the DNA binding affinities or binding site sizes for the H1.1, H1.4 and H1 0 proteins, the differences must be attributed to the different sequences and/or charge and charge distribution in the C-terminal domains of these proteins. It is generally accepted that H1, or linker histone, binds to DNA as it enters and/or exits the nucleosome [10] [11] [12] [13]. Two different models for H1 binding place the H1 protein across the nucleosome with H1 interacting with two or three patches of the nucleosomal DNA on the same side of the nucleosome [14] or alternatively locate the H1 so that it binds to a continuous and more linear linker DNA region [15]. "
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