Physicochemical approach to investigating epigenetic mutations in DNA structures

Abstract Epigenetic regulation is mediated by several mechanisms, including DNA methylation and protein–chromatin interactions, which influence gene expression, structural dynamics, and cellular stress responses. In this review, we highlight advances in physical chemistry applied to molecules carrying epigenetic mutations, such as methylated, acetylated, or otherwise modified nucleic acids and histones, with particular emphasis on the unique contribution of calorimetric methodologies. Techniques such as differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC) provide direct, quantitative insights into the thermodynamic consequences of epigenetic modifications, enabling the analysis of stability, folding transitions, and molecular binding events without the need for labels or chemical probes. Alongside complementary spectroscopic and structural approaches, calorimetry offers a powerful framework for understanding how epigenetic alterations reshape biomolecular energetics and interactions. The review discusses the major mechanisms underlying epigenetic mutations and examines disease‑related implications, while underscoring the pivotal role of calorimetric analyses in uncovering the physicochemical principles that govern these modifications.