DNA Methylation and Chromatin Dynamics Across Aging, Reprogramming, and Early Development: Mechanisms, Disease Trajectories, and Multi-Omics Maps

DNA methylation and chromatin organization undergo profound remodeling during aging, cellular reprogramming, and early development. These transitions reshape cellular identity, developmental competence, and genome stability, yet the causal relationships between methylome remodeling, chromatin accessibility, histone landscapes, higher-order genome architecture, and transcriptional output remain incompletely resolved. Critically, when these transitions go wrong, they underlie a range of non-malignant diseases - from neurodegenerative and progeroid conditions driven by age-associated epigenetic drift, to developmental and imprinting disorders rooted in failures of methylation resetting in the germline and early embryo. Recent advances in single-cell, spatial, and multimodal epigenomics now make it possible to capture both normal and pathological versions of these processes with unprecedented resolution, revealing both conserved principles and context-specific trajectories across species, tissues, and developmental windows. This Research Topic brings together studies that define how DNA methylation and chromatin states are jointly established, erased, inherited, and remodeled during major epigenetic state transitions - and what happens when these processes fail.The Topic will focus on mechanisms, maps, and disease consequences of epigenomic remodeling across three linked contexts: aging, where methylation drift, heterochromatin alteration, and loss of epigenetic fidelity accompany functional decline and contribute to neurodegeneration, tissue dysfunction, and accelerated aging syndromes; reprogramming, where somatic cells overcome epigenetic barriers to regain plasticity, with implications for understanding disease-relevant reprogramming failures and therapeutic rejuvenation; and early development, where genome-wide resetting and lineage specification establish enduring regulatory programs whose disruption underlies imprinting disorders, developmental syndromes, and inherited epigenetic disease. We welcome work that clarifies how methylation dynamics interact with nucleosome positioning, histone modifications, chromatin accessibility, enhancer activity, transposable element regulation, replication timing, and 3D genome organization - both in normal state transitions and in the context of specific non-malignant diseases. Studies that integrate multi-omics datasets to identify transitional cell states, infer regulatory hierarchies, build reference maps of epigenetic remodeling, or connect epigenomic disruption to disease mechanisms are especially encouraged.This Research Topic invites studies that advance understanding of DNA methylation-centered chromatin dynamics during epigenetic resetting, aging-associated drift, and developmental establishment of cell fate, including their direct connections to non-malignant disease. The disease focus of this collection is deliberately distinct from cancer epigenomics, which is addressed in dedicated Research Topics in this journal. Instead, we highlight how disrupted state-transition biology drives conditions such as neurodegeneration, progeroid and accelerated aging syndromes, imprinting disorders, congenital epigenetic diseases, and germline-linked developmental failure. We welcome Original Research, Reviews, Methods, and Perspectives in animal and human systems, and in model organisms where findings illuminate general principles of epigenetic reconfiguration and its pathological consequences.Themes of interest include, but are not limited to:• DNA methylation remodeling during organismal aging, cellular senescence, and rejuvenation, and its role in neurodegenerative disease and tissue aging• Epigenetic barriers and intermediate states during full or partial cellular reprogramming, including reprogramming-based disease modeling• Methylation resetting and chromatin reorganization in the germline, preimplantation embryo, and early lineage specification, and the consequences of resetting failure for imprinting disorders and developmental syndromes• Chromatin and methylation alterations in progeroid syndromes, accelerated aging conditions, and premature epigenetic aging• Disrupted DNA methylation inheritance and its contribution to congenital epigenetic disease and transgenerational epigenetic risk• Coupling of DNA methylation with chromatin accessibility, histone modifications, nucleosome occupancy, and 3D genome architecture in health and non-malignant disease• Mechanisms governing epigenetic memory, erasure, and incomplete resetting across developmental or reprogramming transitions• Single-cell, spatial, and multimodal mapping of methylome-chromatin states across time, in disease and healthy tissue• Comparative analyses of epigenetic trajectories across species, tissues, and developmental stages• Computational frameworks for integrating methylome, transcriptome, chromatin accessibility, and chromatin conformation data, including disease-stratified analyses• Roles of repetitive elements, imprinting control regions, and regulatory non-coding loci in epigenetic remodeling and disease• Methods, resources, and atlas-building studies that generate high-resolution maps of methylation and chromatin state transitions in normal and pathological contextsTo deepen understanding of how epigenetic information is remodeled across the lifespan and reset across cell-fate transitions - and how failures in these processes drive non-malignant disease - we invite submissions that connect mechanism, trajectory, and multi-omics resolution in aging, reprogramming, and early development. Topic editors: Deepika Puri, Pratibha Bhalla, Camelia Alexandra Coada Source: https://www.frontiersin.org/research-topics/81408/dna-methylation-and-chromatin-dynamics-across-aging-reprogramming-and-early-development-mechanisms-disease-trajectories-and-multi-omics-maps