Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and Mechanisms

University Of Tx Md Anderson Can Ctr, Houston TX

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Abstract

Summary/Abstract Rapid advancements in identifying readers, writers, and erasers of epigenetic modifications, particularly in DNA and histone marks, have sparked increased interest in understanding their influence on protein-DNA interactions. This interest is driven not only by the essential role of these interactions in gene expression control but also by the emerging potential of DNA-binding transcription factors (TFs) as druggable targets. In mammals, DNA 5-methylcytosine (5mC) serves as a major epigenetic signal that regulates chromatin structure and, consequently, gene expression. Our research has revealed that many DNA-binding TFs are responsive to the CpG methylation status of their binding sites, including unmodified, 5mC, and successively oxidized forms (5-hydroxymethylC, 5-formylC, and 5-carboxyC). Despite these insights, significant challenges persist in unraveling how specific chromatin regions are targeted for methylation, oxidation, and demethylation, understanding the impact of CpG methylation on genome stability, and elucidating the coordinated effects of DNA and histone modifications on TF binding at DNA-regulatory elements to regulate the expression of specific genes.