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The Role of Linker Histone Mutation in Oncogenesis: Molecular Mechanism and Structural Impact

Gege Liu#, Houfang Zhang#, Yunhui Peng*
Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan, 430079, China
* Corresponding Author: Yunhui Peng. Email: email
# These authors contributed equally to this work
(This article belongs to the Special Issue: Genetic Biomarkers of Cancer: Insights into Molecular and Cellular Mechanisms)

BIOCELL https://doi.org/10.32604/biocell.2025.061470

Received 25 November 2024; Accepted 14 February 2025; Published online 17 March 2025

Abstract

Nucleosomes play a vital role in chromatin organization and gene regulation, acting as key hubs that interact with various chromatin-associated factors through diverse binding mechanisms. Recent research has highlighted the prevalence of mutations in linker histones across different types of cancer, emphasizing their critical involvement in cancer progression. These cancer-associated mutations in linker histones have been shown to disrupt nucleosome stacking and the formation of higher-order chromatin structures, which in turn significantly affect epigenetic regulatory processes. In this review, we provide a comprehensive analysis of how cancer-associated linker histone mutations alter their physicochemical properties, influencing their binding to nucleosomes, and overall chromatin architecture. Additionally, we explore the significant impact of mutations near post-translational modification sites, which further modulate chromatin dynamics and regulatory functions, offering insights into their role in oncogenesis and potential therapeutic targets.

Keywords

Linker histone; H1; epigenetics; histone cancer mutations; chromatin structure; nucleosome

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