Dynamics of Nucleosome Assembly and Effects of DNA Methylation

Lee, Ju‐Yeon; Lee, Jaehyoun; Yue, Hongjun; Lee, Tae Hee

doi:10.1074/jbc.m114.619213

Cited by 43 publications

(46 citation statements)

References 56 publications

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“…6 Briefly, five oligonucleotides were annealed by linearly decreasing the temperature from 95 to 5 °C for 45 min to construct 147 bp Widom 601 nucleosomal DNA 36 with a 20 nucleotides linker that contains biotin at one end (see Figure S1 for the sequence of the DNA). The oligonucleotides including the one labeled with Cy3 were purchased from Integrated DNA Technologies (Coralville, IA).…”

Section: Methodsmentioning

confidence: 99%

Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome

Lee

2017

Biochemistry

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Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation. Two conflicting hypotheses on the requirement for dimer displacement are that nucleosomal DNA needs to be unwrapped before a dimer can displace and that a dimer can displace without DNA unwrapping. In order to test the hypotheses, we employed three-color single-molecule FRET and monitored in a time-resolved manner the early kinetics of H2AH2B dimer dissociation triggered by high salt concentration and by histone chaperone Nap1. The results reveal that dimer displacement requires DNA unwrapping in the vast majority of the nucleosomes in the salt-induced case, while dimer displacement precedes DNA unwrapping in >60% of the nucleosomes in the Nap1-mediated case. We also found that acetylation at histone H4K16 or H3K56 affects the kinetics of Nap1-mediated dimer dissociation and facilitates the process both kinetically and thermodynamically. On the basis of these results, we suggest a mechanism by which histone chaperone facilitates H2A-H2B dimer displacement from the histone core without requiring another factor to unwrap the nucleosomal DNA.

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Section: Methodsmentioning

confidence: 99%

Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome

Lee

2017

Biochemistry

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“…Nucleosome content modulates the accessibility to regulatory regions as well as the presence of specific epigenetic signatures, including histone PTMs and DNA methylation (40)(41)(42). Therefore, we evaluated whether changes in nucleosomal histone H3 accompany the above-described epigenetic profile at the Sp7 promoter during Sp7 gene activation.…”

Section: Myoblasts Myotubesmentioning

confidence: 99%

Tet-Mediated DNA Demethylation Is Required for SWI/SNF-Dependent Chromatin Remodeling and Histone-Modifying Activities That Trigger Expression of the Sp7 Osteoblast Master Gene during Mesenchymal Lineage Commitment

Sepúlveda

Villagra

Montecino

2017

Molecular and Cellular Biology

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Here we assess histone modification, chromatin remodeling, and DNA methylation processes that coordinately control the expression of the bone master transcription factor Sp7 (osterix) during mesenchymal lineage commitment in mammalian cells. We find that Sp7 gene silencing is mediated by DNA methyltransferase1/3 (DNMT1/3)-, histone deacetylase 1/2/4 (HDAC1/2/4)-, Setdb1/Suv39h1-, and Ezh1/2-containing complexes. In contrast, Sp7 gene activation involves changes in histone modifications, accompanied by decreased nucleosome enrichment and DNA demethylation mediated by SWI/SNF- and Tet1/Tet2-containing complexes, respectively. Inhibition of DNA methylation triggers changes in the histone modification profile and chromatin-remodeling events leading to Sp7 gene expression. Tet1/Tet2 silencing prevents Sp7 expression during osteoblast differentiation as it impairs DNA demethylation and alters the recruitment of histone methylase (COMPASS)-, histone demethylase (Jmjd2a/Jmjd3)-, and SWI/SNF-containing complexes to the Sp7 promoter. The dissection of these interconnected epigenetic mechanisms that govern Sp7 gene activation reveals a hierarchical process where regulatory components mediating DNA demethylation play a leading role.

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“…In addition, methylation influences nucleosome formation and stability (25)(26)(27)(28)(29)(30)(31). Though it is known to suppress nucleosome formation (26,27,29,31), opposite results have also been reported (25,28,30). Another study suggests that CpG methylation has no effect on nucleosome stability (32).…”

Section: Introductionmentioning

confidence: 99%

“…For example, it blocks transcription factors (17)(18)(19) or allows binding of methyl-CpGbinding domain proteins (20)(21)(22)(23)(24). In addition, methylation influences nucleosome formation and stability (25)(26)(27)(28)(29)(30)(31). Though it is known to suppress nucleosome formation (26,27,29,31), opposite results have also been reported (25,28,30).…”

Section: Introductionmentioning

confidence: 99%

Effect of Methylation on Local Mechanics and Hydration Structure of DNA

Teng

Hwang

2018

Biophysical Journal

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Cytosine methylation affects mechanical properties of DNA and potentially alters the hydration fingerprint for recognition by proteins. The atomistic origin for these effects is not well understood, and we address this via all-atom molecular dynamics simulations. We find that the stiffness of the methylated dinucleotide step changes marginally, whereas the neighboring steps become stiffer. Stiffening is further enhanced for consecutively methylated steps, providing a mechanistic origin for the effect of hypermethylation. Steric interactions between the added methyl groups and the nonpolar groups of the neighboring nucleotides are responsible for the stiffening in most cases. By constructing hydration maps, we found that methylation also alters the surface hydration structure in distinct ways. Its resistance to deformation may contribute to the stiffening of DNA for deformational modes lacking steric interactions. These results highlight the sequence- and deformational-mode-dependent effects of cytosine methylation.

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Dynamics of Nucleosome Assembly and Effects of DNA Methylation

Cited by 43 publications

References 56 publications

Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome

Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome

Tet-Mediated DNA Demethylation Is Required for SWI/SNF-Dependent Chromatin Remodeling and Histone-Modifying Activities That Trigger Expression of the Sp7 Osteoblast Master Gene during Mesenchymal Lineage Commitment

Effect of Methylation on Local Mechanics and Hydration Structure of DNA

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