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FEBS Letters Oct 2015The nucleosomal subunit organization of chromatin provides a multitude of functions. Nucleosomes elicit an initial ∼7-fold linear compaction of genomic DNA. They... (Review)
Review
The nucleosomal subunit organization of chromatin provides a multitude of functions. Nucleosomes elicit an initial ∼7-fold linear compaction of genomic DNA. They provide a critical mechanism for stable repression of genes and other DNA-dependent activities by restricting binding of trans-acting factors to cognate DNA sequences. Conversely they are engineered to be nearly meta-stable and disassembled (and reassembled) in a facile manner to allow rapid access to the underlying DNA during processes such as transcription, replication and DNA repair. Nucleosomes protect the genome from DNA damaging agents and provide a lattice onto which a myriad of epigenetic signals are deposited. Moreover, vast strings of nucleosomes provide a framework for assembly of the chromatin fiber and higher-order chromatin structures. Thus, in order to provide a foundation for understanding these functions, we present a review of the basic elements of nucleosome structure and stability, including the association of linker histones.
Topics: Animals; Chromatin Assembly and Disassembly; DNA; DNA Repair; DNA Replication; Histones; Humans; Models, Molecular; Nucleic Acid Conformation; Nucleosomes; Protein Structure, Quaternary; Protein Structure, Tertiary
PubMed: 25980611
DOI: 10.1016/j.febslet.2015.05.016 -
Cell Jul 2021Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone... (Review)
Review
Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair.
Topics: Animals; Chromatin; Genome; Humans; Models, Biological; Nucleosomes; Nucleotide Motifs; Transcription Factors
PubMed: 34146479
DOI: 10.1016/j.cell.2021.05.029 -
Current Opinion in Structural Biology Feb 2011Chromatin plays a fundamental role in eukaryotic genomic regulation, and the increasing awareness of the importance of epigenetic processes in human health and disease... (Review)
Review
Chromatin plays a fundamental role in eukaryotic genomic regulation, and the increasing awareness of the importance of epigenetic processes in human health and disease emphasizes the need for understanding the structure and function of the nucleosome. Recent advances in chromatin structural studies, including the first structures of nucleosomes containing the Widom 601 sequence and the structure of a chromatin protein-nucleosome assembly, have provided new insight into stretching of nucleosomal DNA, nucleosome positioning, binding of metal ions, drugs and therapeutic candidates to nucleosomes, and nucleosome recognition by nuclear proteins. These discoveries ensure promising future prospects for unravelling structural attributes of chromatin.
Topics: Animals; DNA; Humans; Nuclear Proteins; Nucleosomes; Protein Binding
PubMed: 21176878
DOI: 10.1016/j.sbi.2010.11.006 -
Chembiochem : a European Journal of... Feb 2021Nucleosomes, which are the fundamental building blocks of chromatin, are highly dynamic, they play vital roles in the formation of higher-order chromatin structures and... (Review)
Review
Nucleosomes, which are the fundamental building blocks of chromatin, are highly dynamic, they play vital roles in the formation of higher-order chromatin structures and orchestrate gene regulation. Nucleosome structures, histone modifications, nucleosome-binding proteins, and their functions are being gradually unravelled with the development of epigenetics. With the continuous development of research approaches such as cryo-EM, FRET and next-generation sequencing for genome-wide analysis of nucleosomes, the understanding of nucleosomes is getting wider and deeper. Herein, we review recent progress in research on nucleosomes and epigenetics, from nucleosome structure to chromatin formation, with a focus on chemical aspects. Basic knowledge of the nucleosome (nucleosome structure, nucleosome position sequence, nucleosome assembly and remodeling), epigenetic modifications, chromatin structure, chemical biology methods and nucleosome, observation nucleosome by AFM, phase separation and nucleosomes are described in this review.
Topics: Animals; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Gene Expression Regulation; Humans; Nucleosomes
PubMed: 32864867
DOI: 10.1002/cbic.202000332 -
Journal of Molecular Biology Mar 2021The regulation of chromatin biology ultimately depends on the manipulation of its smallest subunit, the nucleosome. The proteins that bind and operate on the nucleosome... (Review)
Review
The regulation of chromatin biology ultimately depends on the manipulation of its smallest subunit, the nucleosome. The proteins that bind and operate on the nucleosome do so, while their substrate is part of a polymer embedded in the dense nuclear environment. Their molecular interactions must in some way be tuned to deal with this complexity. Due to the rapid increase in the number of high-resolution structures of nucleosome-protein complexes and the increasing understanding of the cellular chromatin structure, it is starting to become clearer how chromatin factors operate in this complex environment. In this review, we analyze the current literature on the interplay between nucleosome-protein interactions and higher-order chromatin structure. We examine in what way nucleosomes-protein interactions can affect and can be affected by chromatin organization at the oligonucleosomal level. In addition, we review the characteristics of nucleosome-protein interactions that can cause phase separation of chromatin. Throughout, we hope to illustrate the exciting challenges in characterizing nucleosome-protein interactions beyond the nucleosome.
Topics: Chromatin Assembly and Disassembly; Chromobox Protein Homolog 5; Chromosomal Proteins, Non-Histone; DNA; Histones; Humans; Molecular Dynamics Simulation; Nucleic Acid Conformation; Nucleosomes; Polycomb Repressive Complex 2; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Static Electricity
PubMed: 33460684
DOI: 10.1016/j.jmb.2021.166827 -
Chemical Reviews Mar 2015
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Genes Jun 2021The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as... (Review)
Review
The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as transcription, replication, recombination or DNA repair. The DNA sequence has an influence on the position of nucleosomes on genomes, although other factors are also implicated, such as ATP-dependent remodelers or competition of the nucleosome with DNA binding proteins. Different sequence motifs can promote or inhibit the nucleosome formation, thus influencing the accessibility to the DNA. Sequence-encoded nucleosome positioning having functional consequences on cell processes can then be selected or counter-selected during evolution. We review the interplay between sequence evolution and nucleosome positioning evolution. We first focus on the different ways to encode nucleosome positions in the DNA sequence, and to which extent these mechanisms are responsible of genome-wide nucleosome positioning in vivo. Then, we discuss the findings about selection of sequences for their nucleosomal properties. Finally, we illustrate how the nucleosome can directly influence sequence evolution through its interactions with DNA damage and repair mechanisms. This review aims to provide an overview of the mutual influence of sequence evolution and nucleosome positioning evolution, possibly leading to complex evolutionary dynamics.
Topics: Animals; Evolution, Molecular; Humans; Mutation; Nucleosomes; Nucleotide Motifs
PubMed: 34205881
DOI: 10.3390/genes12060851 -
Proceedings of the National Academy of... Nov 1997Archaea contain histones that have primary sequences in common with eukaryal nucleosome core histones and a three-dimensional structure that is essentially only the...
Archaea contain histones that have primary sequences in common with eukaryal nucleosome core histones and a three-dimensional structure that is essentially only the histone fold. Here we report the results of experiments that document that archaeal histones compact DNA in vivo into structures similar to the structure formed by the histone (H3+H4)2 tetramer at the center of the eukaryal nucleosome. After formaldehyde cross-linking in vivo, these archaeal nucleosomes have been isolated from Methanobacterium thermoautotrophicum and Methanothermus fervidus, visualized by electron microscopy on plasmid and genomic DNAs, and shown by immunogold labeling, SDS/PAGE, and immunoblotting to contain archaeal histones, cross-linked into tetramers. Archaeal nucleosomes protect approximately 60 bp of DNA and multiples of approximately 60 bp from micrococcal nuclease digestion, and immunoprecipitation has demonstrated that most, but not all, M. fervidus genomic DNA sequences are associated in vivo with archaeal histones.
Topics: Archaea; Nucleosomes
PubMed: 9356501
DOI: 10.1073/pnas.94.23.12633 -
Trends in Biochemical Sciences Jan 2020Gene regulation in eukaryotes requires the controlled access of sequence-specific transcription factors (TFs) to their sites in a chromatin landscape dominated by... (Review)
Review
Gene regulation in eukaryotes requires the controlled access of sequence-specific transcription factors (TFs) to their sites in a chromatin landscape dominated by nucleosomes. Nucleosomes are refractory to TF binding, and often must be removed from regulatory regions. Recent genomic studies together with in vitro measurements suggest that the nucleosome barrier to TF binding is modulated by dynamic nucleosome unwrapping governed by ATP-dependent chromatin remodelers. Genome-wide occupancy and the regulation of subnucleosomal intermediates have gained recent attention with the application of high-resolution approaches for precision mapping of protein-DNA interactions. We summarize here recent findings on nucleosome substructures and TF binding dynamics, and highlight how unwrapped nucleosomal intermediates provide a novel signature of active chromatin.
Topics: Epigenome; Humans; Nucleosomes; Transcription Factors
PubMed: 31630896
DOI: 10.1016/j.tibs.2019.09.003 -
Journal of Cellular and Molecular... Aug 2021Protein post-translational modifications (PTMs) of histones are ubiquitous regulatory mechanisms involved in many biological processes, including replication,... (Review)
Review
Protein post-translational modifications (PTMs) of histones are ubiquitous regulatory mechanisms involved in many biological processes, including replication, transcription, DNA damage repair and ontogenesis. Recently, many short-chain acylation histone modifications have been identified by mass spectrometry (MS). Lysine succinylation (Ksuc or Ksucc) is a newly identified histone PTM that changes the chemical environment of histones and is similar to other acylation modifications; lysine succinylation appears to accumulate at transcriptional start sites and to correlate with gene expression. Although numerous studies are ongoing, there is a lack of reviews on the Ksuc of histones. Here, we review lysine succinylation sites on histones, including the chemical characteristics and the mechanism by which lysine succinylation influences nucleosomal structure, chromatin dynamics and several diseases and then discuss lysine succinylation regulation to identify theoretical and experimental proof of Ksuc on histones and in diseases to inspire further research into histone lysine succinylation as a target of disease treatment in the future.
Topics: Animals; Histone Code; Humans; Nucleosomes; Succinates
PubMed: 34160884
DOI: 10.1111/jcmm.16676