Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability

Morgan, Aaron; LeGresley, Sarah; Fischer, Christopher J.

doi:10.3390/ijms22010076

Cited by 9 publications

(5 citation statements)

References 137 publications

(282 reference statements)

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“…Different lines of evidence suggested that nucleosome remodelers may interact with nucleosomes at defined yet different sites, including super helical locations SHL+2, SHL−6, and the dyad axis (reviewed in Morgan et al [2021] ). In particular, recent cryo-EM analysis showed that human SMARCAD1 engages in an unusual contact with nucleosomes at the dyad axis, but the overall resolution was too low to unambiguously dock the Fun30 ATPase and especially to detect the SAM-key ( Markert et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler

et al. 2023

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Fun30 is the prototype of the Fun30-SMARCAD1-ETL subfamily of nucleosome remodelers involved in DNA repair and gene silencing. These proteins appear to act as single-subunit nucleosome remodelers, but their molecular mechanisms are, at this point, poorly understood. Using multiple sequence alignment and structure prediction, we identify an evolutionarily conserved domain that is modeled to contain a SAM-like fold with one long, protruding helix, which we term SAM-key. Deletion of the SAM-key within budding yeast Fun30 leads to a defect in DNA repair and gene silencing similar to that of thefun30Δ mutant. In vitro, Fun30 protein lacking the SAM-key is able to bind nucleosomes but is deficient in DNA-stimulated ATPase activity and nucleosome sliding and eviction. A structural model based on AlphaFold2 prediction and verified by crosslinking-MS indicates an interaction of the long SAM-key helix with protrusion I, a subdomain located between the two ATPase lobes that is critical for control of enzymatic activity. Mutation of the interaction interface phenocopies the domain deletion with a lack of DNA-stimulated ATPase activation and a nucleosome-remodeling defect, thereby confirming a role of the SAM-key helix in regulating ATPase activity. Our data thereby demonstrate a central role of the SAM-key domain in mediating the activation of Fun30 catalytic activity, thus highlighting the importance of allosteric activation for this class of enzymes.

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Section: Resultsmentioning

confidence: 99%

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler

et al. 2023

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“…Histone H1 binds DNA near the entry and exit sites along the nucleosome core particles and functions to stabilize the nucleosome and compact the chromatin fiber ( 66 – 69 ). Chromatin remodelers actively alter nucleosome positioning and may promote or prevent HP1 interactions ( 70 – 73 ). Further theoretical development is needed to address the interplay between HP1 binding and nucleosome remodelers, given the non-equilibrium nature of their actions.…”

Section: Discussionmentioning

confidence: 99%

Physical modeling of nucleosome clustering in euchromatin resulting from interactions between epigenetic reader proteins

Wakim,

Spakowitz

2024

Proc. Natl. Acad. Sci. U.S.A.

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Euchromatin is an accessible phase of genetic material containing genes that encode proteins with increased expression levels. The structure of euchromatin in vitro has been described as a 30-nm fiber formed from ordered nucleosome arrays. However, recent advances in microscopy have revealed an in vivo euchromatin architecture that is much more disordered, characterized by variable-length linker DNA and sporadic nucleosome clusters. In this work, we develop a theoretical model to elucidate factors contributing to the disordered in vivo architecture of euchromatin. We begin by developing a 1D model of nucleosome positioning that captures the interactions between bound epigenetic reader proteins to predict the distribution of DNA linker lengths between adjacent nucleosomes. We then use the predicted linker lengths to construct 3D chromatin configurations consistent with the physical properties of DNA within the nucleosome array, and we evaluate the distribution of nucleosome cluster sizes in those configurations. Our model reproduces experimental cluster-size distributions, which are dramatically influenced by the local pattern of epigenetic marks and the concentration of reader proteins. Based on our model, we attribute the disordered arrangement of euchromatin to the heterogeneous binding of reader proteins and subsequent short-range interactions between bound reader proteins on adjacent nucleosomes. By replicating experimental results with our physics-based model, we propose a mechanism for euchromatin organization in the nucleus that impacts gene regulation and the maintenance of epigenetic marks.

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“…Therefore, Hyde et al [ 11 ] suggested that epigenetics works as the interface between the individual and its environment to provide phenotypic plasticity to increase their adaptation capabilities [ 11 ]. Some of the epigenetic mechanisms that act in modulating gene expression are DNA methylation [ 15 ], DNA acetylation [ 67 ], histone modifications [ 68 ], nucleosome repositioning [ 69 ], and small interfering RNAs [ 16 ]. These biological mechanisms help cells to differentiate not only morphologically, but also functionally, controlling the genomic regions that will be accessed and/or expressed.…”

Section: Epigeneticsmentioning

confidence: 99%

How Epigenetics Can Enhance Pig Welfare?

Silva

Araujo

Pértille

et al. 2021

Animals

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Epigenetics works as an interface between the individual and its environment to provide phenotypic plasticity to increase individual adaptation capabilities. Recently, a wide variety of epi-genetic findings have indicated evidence for its application in the development of putative epi-biomarkers of stress in farm animals. The purpose of this study was to evaluate previously reported stress epi-biomarkers in swine and encourage researchers to investigate potential paths for the development of a robust molecular tool for animal welfare certification. In this literature review, we report on the scientific concerns in the swine production chain, the management carried out on the farms, and the potential implications of these practices for the animals’ welfare and their epigenome. To assess reported epi-biomarkers, we identified, from previous studies, potentially stress-related genes surrounding epi-biomarkers. With those genes, we carried out a functional enrichment analysis of differentially methylated regions (DMRs) of the DNA of swine subjected to different stress-related conditions (e.g., heat stress, intrauterine insult, and sanitary challenges). We identified potential epi-biomarkers for target analysis, which could be added to the current guidelines and certification schemes to guarantee and certify animal welfare on farms. We believe that this technology may have the power to increase consumers’ trust in animal welfare.

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Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability

Cited by 9 publications

References 137 publications

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler

A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler

Physical modeling of nucleosome clustering in euchromatin resulting from interactions between epigenetic reader proteins

How Epigenetics Can Enhance Pig Welfare?

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