Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2

Ortega-Alarcón, David; Clavería-Gimeno, Rafael; Vega, Sonia; Jorge-Torres, Olga C.; Esteller, Manel; Abián, Olga; Velázquez‐Campoy, Adrián

doi:10.1016/j.ijbiomac.2023.123373

Cited by 3 publications

(3 citation statements)

References 56 publications

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“… 62 The interaction of MeCP2 with hydroxymethylated DNA has a different thermodynamic signature, compared to that of methylated or unmethylated DNA. 181 These studies show the complex regulatory role of MeCP2 in gene transcription through read mCpG, mCpA, and hmCpA signals.…”

Section: Methylation In Neurological Disorders Cancer and Agingmentioning

confidence: 89%

Methylation across the central dogma in health and diseases: new therapeutic strategies

Liu,

Zhao,

et al. 2023

Sig Transduct Target Ther

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The proper transfer of genetic information from DNA to RNA to protein is essential for cell-fate control, development, and health. Methylation of DNA, RNAs, histones, and non-histone proteins is a reversible post-synthesis modification that finetunes gene expression and function in diverse physiological processes. Aberrant methylation caused by genetic mutations or environmental stimuli promotes various diseases and accelerates aging, necessitating the development of therapies to correct the disease-driver methylation imbalance. In this Review, we summarize the operating system of methylation across the central dogma, which includes writers, erasers, readers, and reader-independent outputs. We then discuss how dysregulation of the system contributes to neurological disorders, cancer, and aging. Current small-molecule compounds that target the modifiers show modest success in certain cancers. The methylome-wide action and lack of specificity lead to undesirable biological effects and cytotoxicity, limiting their therapeutic application, especially for diseases with a monogenic cause or different directions of methylation changes. Emerging tools capable of site-specific methylation manipulation hold great promise to solve this dilemma. With the refinement of delivery vehicles, these new tools are well positioned to advance the basic research and clinical translation of the methylation field.

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Section: Methylation In Neurological Disorders Cancer and Agingmentioning

confidence: 89%

Methylation across the central dogma in health and diseases: new therapeutic strategies

Liu,

Zhao,

et al. 2023

Sig Transduct Target Ther

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“…A particular thermodynamic signature of binding hmC-DNA, compared to methylated or unmethylated DNA, has been shown for MeCP2; mutations affecting the hmCpG -MeCP2 interactions are associated with the phenotype of the Rett syndrome. 148 UHRF2 has been shown to use a base-flipping mechanism, first discovered in a DNA MTase, 149,150 for exclusive recognition and enhanced binding of hmC-DNA. 149 Altering the target specificity or de novo engineering artificial hmC binders for biotechnological applications have been demonstrated for TALEs 151 and MeCp2.…”

Section: Protein-dna Interactionsmentioning

confidence: 99%

5-Hydroxymethylcytosine: the many faces of the sixth base of mammalian DNA

Kriukienė,

Tomkuvienė,

Klimašauskas

2024

Chem. Soc. Rev.

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“…We have studied the interaction of several MeCP2 constructs (MBD, NTD-MBD, NTD-MBD-ID, NTD-MBD-ID-TRD, NTD-MBD-ID-TRD-CTDα and NTD-MBD-ID-TRD-CTDα-CTDβ) with unmethylated, methylated, and hydroxymethylated DNA ( 20–25 ). In addition, we have studied the effect of two primary RTT-associated mutations: R106W and R133C.…”

Section: Introductionmentioning

confidence: 99%

Extending MeCP2 interactome: canonical nucleosomal histones interact with MeCP2

Ortega-Alarcon,

Claveria-Gimeno,

Vega

et al. 2024

Nucleic Acids Research

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MeCP2 is a general regulator of transcription involved in the repression/activation of genes depending on the local epigenetic context. It acts as a chromatin regulator and binds with exquisite specificity to gene promoters. The set of epigenetic marks recognized by MeCP2 has been already established (mainly, cytosine modifications in CpG and CpA), as well as many of the constituents of its interactome. We unveil a new set of interactions for MeCP2 with the four canonical nucleosomal histones. MeCP2 interacts with high affinity with H2A, H2B, H3 and H4. In addition, Rett syndrome associated mutations in MeCP2 and histone epigenetic marks modulate these interactions. Given the abundance and the structural/functional relevance of histones and their involvement in epigenetic regulation, this new set of interactions and its modulating elements provide a new addition to the ‘alphabet’ for this epigenetic reader.

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Unexpected thermodynamic signature for the interaction of hydroxymethylated DNA with MeCP2

Cited by 3 publications

References 56 publications

Methylation across the central dogma in health and diseases: new therapeutic strategies

Methylation across the central dogma in health and diseases: new therapeutic strategies

5-Hydroxymethylcytosine: the many faces of the sixth base of mammalian DNA

Extending MeCP2 interactome: canonical nucleosomal histones interact with MeCP2

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