Examining histone modification crosstalk using immobilized libraries established from ligation-ready nucleosomes

Pelaz, Diego Aparicio; Yerkesh, Zhadyra; Kirchgäßner, Sören; Mahler, Henriette; Kharchenko, Vladlena; Azhibek, Dulat; Jaremko, Mariusz; Mootz, Henning D.; Jaremko, Łukasz; Schwarzer, Dirk; Fischle, Wolfgang

doi:10.1039/d0sc03407j

Cited by 20 publications

(14 citation statements)

References 45 publications

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“…Interestingly, mutation of H3S28 to E within the 187-bp-nucleosome without any additional modification/ mutation to the N-terminal portion of the H3 tail led to changes in chemical shift and a decrease in residue level τ C values for the majority of the tail. 35 Importantly, these effects were only seen in the context of the nucleosome, with none of these modifications leading to a change in the dynamics of the tail peptide. The presence of charge altering modifications on the histone tail can attenuate the association of the tail with DNA and promote binding of reader domains or additional modification.…”

Section: Residue Specific Rotational Correlation Times (τ C )mentioning

confidence: 99%

“…Dual phosphorylation of H3S10 and H3S28 led to an increase in the dynamics of residues 3–31 with smaller effects on residues 32–36. Interestingly, mutation of H3S28 to E within the 187-bp-nucleosome without any additional modification/mutation to the N-terminal portion of the H3 tail led to changes in chemical shift and a decrease in residue level τ C values for the majority of the tail . Importantly, these effects were only seen in the context of the nucleosome, with none of these modifications leading to a change in the dynamics of the tail peptide.…”

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confidence: 99%

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Visualizing Conformational Ensembles of the Nucleosome by NMR

Musselman

Kutateladze

2022

ACS Chem. Biol.

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The formation of chromatin not only compacts the eukaryotic genome into the nucleus but also provides a mechanism for the regulation of all DNA templated processes. Spatial and temporal modulation of the chromatin structure is critical in such regulation and involves fine-tuned functioning of the basic subunit of chromatin, the nucleosome. It has become apparent that the nucleosome is an inherently dynamic system, but characterization of these dynamics at the atomic level has remained challenging. NMR spectroscopy is a powerful tool for investigating the conformational ensemble and dynamics of proteins and protein complexes, and recent advances have made the study of large systems possible. Here, we review recent studies which utilize NMR spectroscopy to uncover the atomic level conformation and dynamics of the nucleosome and provide a better understanding of the importance of these dynamics in key regulatory events.

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Section: Residue Specific Rotational Correlation Times (τ C )mentioning

confidence: 99%

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confidence: 99%

Visualizing Conformational Ensembles of the Nucleosome by NMR

Musselman

Kutateladze

2022

ACS Chem. Biol.

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“…Methylated histone residues are recognized by several protein domains such as plant homeodomain zinc fingers, Tudor domains, or WD40 repeats. While histone acetylation is usually associated with transcriptional activation, histone methylation has various functions, depending on the type of histone, the type of amino acid, the degree of modification, and another histone’s PTMs in the vicinity [ 60 , 61 ]. For example, in the promoter region, di- or tri-methylation of histone H3 at lysine 4 (H3K4me2, H3K4me3) is associated with transcriptional activation; in contrast, H3K27me3 and H3K9me3 are transcriptionally repressive marks [ 62 ].…”

Section: Epigenetics: Another Layer Of Information In Gene Expression Regulationmentioning

confidence: 99%

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Dobre

Constantin

Costache

et al. 2021

JPM

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Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

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“…These modifications can alter DNA-histone contacts and their conformation, and consequently affect their intrinsic properties, chromatin organization, and underlying transcriptional processes. 6,[10][11][12][13][14][15] The range of known histone PTMs that influence the structural and functional state of chromosomes, and the chromatin-based processes such as gene expression, transcription, DNA replication, and DNA repair, continues to grow. 6,10 In cancer, misregulation of chromatin-based processes leads to inappropriate inactivation of tumor suppressors.…”

Section: Introductionmentioning

confidence: 99%