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
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.
Available from: Alexandre Berr
- "However, nucleosomes are not merely static but highly dynamic entities. Indeed, nucleosomes can be moved, stabilized/destabilized, disassembled/reassembled at particular genome locations in response to specific environmental signals or developmental cues . This dynamic leads to a wide range of chromatin condensation states modulating the DNA accessibility, with euchromatin, being relaxed, and heterochromatin, being compacted. "
Available from: Jianrong Zhang
- "There are five families of histones known to date: H2A, H2B, H3, and H4, which are known as " core histones, " and histone H1 and its homolog H5, which are known as the linker histones   . Histones are the basic structural elements in the nucleosome, which contains one H3/H4 tetramer and two H2A/H2B dimers, while H1 binds to nonnucleosomal DNA and facilitates numerous nucleosomes to form higherorder chromatin structures  . Even though histones are extremely inert in the nucleus, they lead to significant pathogenic effects outside of the cells. "
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ABSTRACT: Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.
- "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.
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