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Journal of Molecular Biology Jul 2021Chromatin remodelers act to regulate multiple cellular processes, such as transcription and DNA repair, by controlling access to genomic DNA. Four families of chromatin... (Review)
Review
Chromatin remodelers act to regulate multiple cellular processes, such as transcription and DNA repair, by controlling access to genomic DNA. Four families of chromatin remodelers have been identified in yeast, each with non-redundant roles within the cell. There has been a recent surge in structural models of chromatin remodelers in complex with their nucleosomal substrate. These structural studies provide new insight into the mechanism of action for individual chromatin remodelers. In this review, we summarize available data for the structure and mechanism of action of the four chromatin remodeling complex families.
Topics: Chromatin; Chromatin Assembly and Disassembly; Gene Expression Regulation; Humans; Nucleosomes; Structure-Activity Relationship; Yeasts
PubMed: 33711345
DOI: 10.1016/j.jmb.2021.166929 -
Mutation Research 2020
Topics: Animals; Cell Nucleus; Chromatin; DNA Damage; DNA Repair; Humans
PubMed: 32846362
DOI: 10.1016/j.mrfmmm.2020.111721 -
Epigenetics & Chromatin Oct 2021The review begins with a concise description of the principles of phase separation. This is followed by a comprehensive section on phase separation of chromatin, in... (Review)
Review
The review begins with a concise description of the principles of phase separation. This is followed by a comprehensive section on phase separation of chromatin, in which we recount the 60 years history of chromatin aggregation studies, discuss the evidence that chromatin aggregation intrinsically is a physiologically relevant liquid-solid phase separation (LSPS) process driven by chromatin self-interaction, and highlight the recent findings that under specific solution conditions chromatin can undergo liquid-liquid phase separation (LLPS) rather than LSPS. In the next section of the review, we discuss how certain chromatin-associated proteins undergo LLPS in vitro and in vivo. Some chromatin-binding proteins undergo LLPS in purified form in near-physiological ionic strength buffers while others will do so only in the presence of DNA, nucleosomes, or chromatin. The final section of the review evaluates the solid and liquid states of chromatin in the nucleus. While chromatin behaves as an immobile solid on the mesoscale, nucleosomes are mobile on the nanoscale. We discuss how this dual nature of chromatin, which fits well the concept of viscoelasticity, contributes to genome structure, emphasizing the dominant role of chromatin self-interaction.
Topics: Cell Nucleus; Chromatin; DNA; Nucleosomes
PubMed: 34717733
DOI: 10.1186/s13072-021-00424-5 -
Current Opinion in Genetics &... Apr 2014Supercoiling is a fundamental property of DNA and chromatin. It is modulated by polymerase and topoisomerase activities and, through regulated constraint, by... (Review)
Review
Supercoiling is a fundamental property of DNA and chromatin. It is modulated by polymerase and topoisomerase activities and, through regulated constraint, by DNA/chromatin binding proteins. As a non-covalent and elusive topological modification, supercoiling has proved intractable to research despite being a crucial regulator of nuclear structure and function. Recent studies have improved our understanding of the formation, regulation and organisation of supercoiling domains in vivo, and reinforce the prospect that the propagation of supercoiling can influence local and global chromatin structure. However, to further our understanding the development of new experimental tools and models are required to better dissect the mechanics of this key topological regulator.
Topics: Animals; Chromatin; DNA; DNA-Binding Proteins; Humans; Nucleic Acid Conformation
PubMed: 24584092
DOI: 10.1016/j.gde.2013.10.013 -
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 -
Genes & Development Nov 2017Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and... (Review)
Review
Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA. We review the requirements and mechanisms that cause chromatin relocation, enhanced mobility, and chromatin unfolding as a consequence of genotoxic lesions. An intriguing link has been established recently between enhanced chromatin dynamics and histone loss.
Topics: Chromatin; DNA Damage; DNA Repair; Histones; Nucleosomes
PubMed: 29284710
DOI: 10.1101/gad.307702.117 -
Mutation Research 2020The nucleus is the organelle in the cell that contains the genome and its associate proteins which is collectively called chromatin. New work has shown that chromatin... (Review)
Review
The nucleus is the organelle in the cell that contains the genome and its associate proteins which is collectively called chromatin. New work has shown that chromatin and its compaction level, dictated largely through histone modification state, provides rigidity to protect and stabilize the nucleus. Alterations in chromatin, its mechanics, and downstream loss of nuclear shape and stability are hallmarks of human disease. Weakened nuclear mechanics and abnormal morphology have been shown to cause rupturing of the nucleus which results in nuclear dysfunction including DNA damage. Thus, the rigidity provided by chromatin to maintain nuclear mechanical stability also provides its own protection from DNA damage via compartmentalization maintenance.
Topics: Cell Nucleus; Chromatin; DNA Damage; DNA Repair; Genome, Human; Humans; Mechanotransduction, Cellular
PubMed: 32590202
DOI: 10.1016/j.mrfmmm.2020.111712 -
Current Opinion in Structural Biology Aug 2022DNA methylation plays a vital role in epigenetic regulation in both plants and animals, and typically occurs at the 5-carbon position of the cytosine pyrimidine ring... (Review)
Review
DNA methylation plays a vital role in epigenetic regulation in both plants and animals, and typically occurs at the 5-carbon position of the cytosine pyrimidine ring within the CpG dinucleotide steps. Cytosine methylation can alter DNA's geometry, mechanical and physico-chemical properties - thus influencing the molecular signaling events vital for transcription, replication and chromatin remodeling. Despite the profound effect cytosine methylation can have on DNA, the underlying atomistic mechanisms remain enigmatic. Many studies so far have produced controversial findings on how cytosine methylation dictates DNA flexibility and accessibility, nucleosome stability and dynamics. Here, we review the most recent experimental and computational studies that provide precise characterization of structure and function of cytosine methylation and its versatile roles in modulating DNA mechanics, nucleosome and chromatin structure, stability and dynamics. Moreover, the review briefly discusses the relationship between DNA methylation and nucleosome positioning, and the crosstalk between DNA methylation and histone tail modifications.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; CpG Islands; Cytosine; DNA; DNA Methylation; Epigenesis, Genetic; Nucleosomes
PubMed: 35914496
DOI: 10.1016/j.sbi.2022.102430 -
Science China. Life Sciences May 2012Archaea, along with Bacteria and Eukarya, are the three domains of life. In all living cells, chromatin proteins serve a crucial role in maintaining the integrity of the... (Review)
Review
Archaea, along with Bacteria and Eukarya, are the three domains of life. In all living cells, chromatin proteins serve a crucial role in maintaining the integrity of the structure and function of the genome. An array of small, abundant and basic DNA-binding proteins, considered candidates for chromatin proteins, has been isolated from the Euryarchaeota and the Crenarchaeota, the two major phyla in Archaea. While most euryarchaea encode proteins resembling eukaryotic histones, crenarchaea appear to synthesize a number of unique DNA-binding proteins likely involved in chromosomal organization. Several of these proteins (e.g., archaeal histones, Sac10b homologs, Sul7d, Cren7, CC1, etc.) have been extensively studied. However, whether they are chromatin proteins and how they function in vivo remain to be fully understood. Future investigation of archaeal chromatin proteins will lead to a better understanding of chromosomal organization and gene expression in Archaea and provide valuable information on the evolution of DNA packaging in cellular life.
Topics: Amino Acid Sequence; Archaeal Proteins; Chromatin; Models, Molecular; Molecular Sequence Data; Phylogeny; Sequence Homology, Amino Acid
PubMed: 22645082
DOI: 10.1007/s11427-012-4322-y -
Molecular and Cellular Biology Oct 2016The Keystone Symposium on Chromatin and Epigenetics, organized by Luciano Di Croce (Center for Genomic Regulation, Spain) and Yang Shi (Harvard Medical School, USA),... (Review)
Review
The Keystone Symposium on Chromatin and Epigenetics, organized by Luciano Di Croce (Center for Genomic Regulation, Spain) and Yang Shi (Harvard Medical School, USA), took place 20 to 24 March 2016 at Whistler (British Columbia, Canada). The symposium brought together some of the most outstanding scientists studying how chromatin structure and epigenetic mechanisms regulate gene function in both development and disease. Junior scientists had the opportunity to interact with experienced researchers by presenting their work and discussing ideas and novel hypotheses. In order to foster interaction and networking, the scientific agenda was balanced with an extended social agenda. This meeting review describes several of the most provocative and exciting talks from the symposium, revealing how fast this research field is evolving and the profound impact it will have on human health.
Topics: Animals; Chromatin; Chromatin Assembly and Disassembly; Congresses as Topic; Epigenesis, Genetic; Gene Expression Regulation; Humans; Neoplasms
PubMed: 27402863
DOI: 10.1128/MCB.00328-16