Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation

Vinciguerra, M ORCID: 0000-0002-1768-3894 and Tsoneva, DK (2025) Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation. Frontiers in Immunology, 16.

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Abstract

Histone variants are specialized isoforms of histone proteins that play crucial roles in regulating chromatin structure and function, influencing transcription, DNA repair, and cell cycle progression. Their dynamic incorporation into nucleosomes impacts gene expression and cellular identity, particularly in the context of inflammation during cell dedifferentiation and transdifferentiation. This mini-review provides a comprehensive overview of the role of histone variants in these processes, highlighting their significance in modulating inflammatory responses and cellular plasticity. We discuss mechanisms by which histone variants influence chromatin architecture and gene regulation, the interplay between histone variants and inflammatory pathways, and the specific roles of key histone variants such as H3.3, H2A.Z, and MacroH2A in dedifferentiation and transdifferentiation. Additionally, we explore the potential therapeutic implications of targeting histone variants to modulate inflammation and cellular plasticity in diseases like cancer and chronic inflammatory conditions. By summarizing existing knowledge and identifying gaps in understanding, this review underscores the importance of histone variants in inflammation-related cell plasticity and suggests future research directions further elucidating their roles and therapeutic potential.

Item Type:	Article
Uncontrolled Keywords:	Animals; Humans; Inflammation; Histones; Gene Expression Regulation; Cell Dedifferentiation; Cell Transdifferentiation; Cell Plasticity; differentiation; epigenetics; histone variants; inflammation; stem cells; Humans; Cell Transdifferentiation; Histones; Inflammation; Cell Dedifferentiation; Animals; Cell Plasticity; Gene Expression Regulation; 3101 Biochemistry and Cell Biology; 31 Biological Sciences; Genetics; Cancer; 1.1 Normal biological development and functioning; 2.1 Biological and endogenous factors; Generic health relevance; Inflammatory and immune system; Humans; Cell Transdifferentiation; Histones; Inflammation; Cell Dedifferentiation; Animals; Cell Plasticity; Gene Expression Regulation; 1107 Immunology; 1108 Medical Microbiology; 3101 Biochemistry and cell biology; 3105 Genetics; 3204 Immunology
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	Frontiers Media
Date of acceptance:	16 June 2025
Date of first compliant Open Access:	29 August 2025
Date Deposited:	29 Aug 2025 09:37
Last Modified:	29 Aug 2025 09:45
DOI or ID number:	10.3389/fimmu.2025.1619100
URI:	https://researchonline.ljmu.ac.uk/id/eprint/27018

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