Epigenetic Memory in Human Diseases: Acquired Chromatin States as Targetable Drivers of Disease Evolution
5 affiliations
- 1Integral Centre of Excellence for Interdisciplinary Research (ICEIR), Integral University, Lucknow 226026, India
- 2Department of Biosciences, Integral University, Lucknow 226026, India
- 3Department of Biotechnology, Yeungnam University, 280 Daehak-ro, Gyeongsan 38541, Republic of Korea
- 4Department of Bioengineering, Integral University, Lucknow 226026, India
- 5Hamad Medical Corporation, Doha 3050, Qatar
Abstract
Clinical heterogeneity remains a major challenge across human diseases, where patients with similar genetic backgrounds frequently exhibit striking differences in disease progression, therapeutic response and clinical outcome. Increasing evidence indicates that these differences cannot be explained by genetic variation alone, positioning epigenetic memory as a critical non-genetic determinant of disease behavior. Epigenetic memory refers to the stable yet reversible propagation of transcriptional states through mechanisms including DNA methylation, histone modifications, chromatin accessibility, enhancer dynamics and higher-order chromatin organization. In this review, we synthesize emerging mechanistic and translational evidence demonstrating how epigenetic memory integrates environmental, metabolic, inflammatory, infectious and therapeutic cues into persistent cellular programs that drive inter-patient, intra-tumoral and temporal heterogeneity. We discuss its disease-specific manifestations across cancer, immunological, neurological, and metabolic disorders, with particular emphasis on cellular plasticity, stemness, immune evasion, drug-tolerant persister states and relapse. Furthermore, we highlight recent advances in single-cell and spatial epigenomics, liquid-biopsy-based epigenetic biomarkers, CRISPR-mediated epigenome editing and targeted chromatin therapies that collectively establish epigenetic memory as both a measurable biomarker and a therapeutically actionable vulnerability. By framing epigenetic memory as a dynamic interface between genome and environment, this review provides a unified conceptual framework for understanding disease evolution and advancing precision epigenetic medicine.
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BibTeX
@article{khan2026epigenetic,
title = {{Epigenetic Memory in Human Diseases: Acquired Chromatin States as Targetable Drivers of Disease Evolution}},
author = {Shahper Nazeer Khan and Danishuddin and Salamatu Tijjani Isah and Mohammed Haris Siddiqui and Aamir Ahmad and Jong-Joo Kim},
journal = {Biomolecules},
year = {2026},
month = oct,
doi = {10.3390/biom16101463},
url = {https://www.mdpi.com/2218-273X/16/10/1463},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Epigenetic Memory in Human Diseases: Acquired Chromatin States as Targetable Drivers of Disease Evolution
AU - Shahper Nazeer Khan
AU - Danishuddin
AU - Salamatu Tijjani Isah
AU - Mohammed Haris Siddiqui
AU - Aamir Ahmad
AU - Jong-Joo Kim
PY - 2026
DA - 2026/10/01
JO - Biomolecules
DO - 10.3390/biom16101463
UR - https://www.mdpi.com/2218-273X/16/10/1463
AB - Clinical heterogeneity remains a major challenge across human diseases, where patients with similar genetic backgrounds frequently exhibit striking differences in disease progression, therapeutic response and clinical outcome. Increasing evidence indicates that these differences cannot be explained by genetic variation alone, positioning epigenetic memory as a critical non-genetic determinant of disease behavior. Epigenetic memory refers to the stable yet reversible propagation of transcriptional states through mechanisms including DNA methylation, histone modifications, chromatin accessibility, enhancer dynamics and higher-order chromatin organization. In this review, we synthesize emerging mechanistic and translational evidence demonstrating how epigenetic memory integrates environmental, metabolic, inflammatory, infectious and therapeutic cues into persistent cellular programs that drive inter-patient, intra-tumoral and temporal heterogeneity. We discuss its disease-specific manifestations across cancer, immunological, neurological, and metabolic disorders, with particular emphasis on cellular plasticity, stemness, immune evasion, drug-tolerant persister states and relapse. Furthermore, we highlight recent advances in single-cell and spatial epigenomics, liquid-biopsy-based epigenetic biomarkers, CRISPR-mediated epigenome editing and targeted chromatin therapies that collectively establish epigenetic memory as both a measurable biomarker and a therapeutically actionable vulnerability. By framing epigenetic memory as a dynamic interface between genome and environment, this review provides a unified conceptual framework for understanding disease evolution and advancing precision epigenetic medicine.
SN - 2218-273X
ER -