Review

Authors: Alexis A Reyes, Ryan D Marcum, Yuan He...

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

Authors: Fangfei Qin, Boyuan Li, Hui Wang...

A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and β-hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr's gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the "metabolites-modification-regulation" axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.

Topics: Acylation; Chromatin; Chromosome Mapping; Histones; Proteome; Cell Survival

PubMed: 36868209
DOI: 10.1016/j.cell.2023.02.007

Authors: Ming Kuang, Yingchi Zhao, Haitao Yu...

A rapid induction of antiviral genes is critical for eliminating viruses, which requires activated transcription factors and opened chromatins to initiate transcription. However, it remains elusive how the accessibility of specific chromatin is regulated during infection. Here, we found that XAF1 functioned as an epigenetic regulator that liberated repressed chromatin after infection. Upon RNA virus infection, MAVS recruited XAF1 and TBK1. TBK1 phosphorylated XAF1 at serine-252 and promoted its nuclear translocation. XAF1 then interacted with TRIM28 with the guidance of IRF1 to the specific locus of antiviral genes. XAF1 de-SUMOylated TRIM28 through its PHD domain, which led to increased accessibility of the chromatin and robust induction of antiviral genes. XAF1-deficient mice were susceptible to RNA virus due to impaired induction of antiviral genes. Together, XAF1 acts as an epigenetic regulator that promotes the opening of chromatin and activation of antiviral immunity by targeting TRIM28 during infection.

Topics: Animals; Mice; Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Chromatin; Epigenomics; Immunity; RNA; RNA Virus Infections

PubMed: 37595039
DOI: 10.1126/sciadv.adg5211

Authors: Maëlle Locatelli, Pierre-Alexandre Vidi

Topics: Animals; Cell Nucleus; Chromatin; DNA Damage; DNA Repair; Humans

PubMed: 32846362
DOI: 10.1016/j.mrfmmm.2020.111721

Review

Authors: ZhenFeng Zhang, Li Guo, Li Huang...

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

Review

Authors: Jeffrey C Hansen, Kazuhiro Maeshima, Michael J Hendzel...

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

Review

Authors: Michael H Hauer, Susan M Gasser

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

Review

Authors: Nick Gilbert, James Allan

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

Review

Authors: Jessica A Downs, Susan M Gasser

The substrate for the repair of DNA damage in living cells is not DNA but chromatin. Chromatin bears a range of modifications, which in turn bind ligands that compact or open chromatin structure, and determine its spatial organization within the nucleus. In some cases, RNA in the form of RNA:DNA hybrids or R-loops modulates DNA accessibility. Each of these parameters can favor particular pathways of repair. Chromatin or nucleosome remodelers are key regulators of chromatin structure, and a number of remodeling complexes are implicated in DNA repair. We cover novel insights into the impact of chromatin structure, nuclear organization, R-loop formation, nuclear actin, and nucleosome remodelers in DNA double-strand break repair, focusing on factors that alter repair functional upon ablation.

Topics: DNA Breaks, Double-Stranded; Chromatin Assembly and Disassembly; Humans; DNA Repair; Animals; Chromatin; Nucleosomes

PubMed: 39083951
DOI: 10.1016/j.ceb.2024.102405

Review

Authors: Andrew D Stephens

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