Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity - Academic article

Sep 21, 2026

Uploaded by Maeve

Histone chaperones regulate chromatin dynamics by coordinating nucleosome assembly and disassembly, supporting proper gene expression and preserving genomic stability. They also block aberrant histone interactions before chromatin formation. When chaperone function is disrupted, genomic instability can drive cancer pathogenesis. The review explains how histone chaperones become dysregulated across tumors through expression changes, mutations, or abnormal interactions, and describes molecular mechanisms linking them to oncogenic factors that sustain cancer survival and growth.

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Review Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity Jiho Lee and Xiucong Bao * Citation: Lee, J.; Bao, X. Comparative Review on Cancer Pathology from Aberrant Histone Chaperone Activity. Int. J. Mol. Sci. 2024, 25, 6403. [https://](https://)[ ](https://)[doi.org/10.3390/ijms25126403](doi.org/10.3390/ijms25126403) Academic Editor: Stefano Papa Received: 24 April 2024 Revised: 3 June 2024 Accepted: 6 June 2024 Published: 10 June 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . School of Biomedical Sciences, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; jhlee01@connect.hku.hk * Correspondence: baoxc@hku.hk Abstract: Histone chaperones are integral to chromatin dynamics, facilitating the assembly and disassembly of nucleosomes, thereby playing a crucial role in regulating gene expression and maintaining genomic stability. Moreover, they prevent aberrant histone interactions prior to chromatin assembly. Disruption in histone chaperone function may result in genomic instability, which is implicated in pathogenesis. This review aims to elucidate the role of histone chaperones in cancer pathologies and explore their potential as therapeutic targets. Histone chaperones have been found to be dysregulated in various cancers, with alterations in expression levels, mutations, or aberrant interactions leading to tumorigenesis and cancer progression. In addition, this review intends to highlight the molecular mechanisms of interactions between histone chaperones and oncogenic factors, underscoring their roles in cancer cell survival and proliferation. The dysregulation of histone chaperones is significantly correlated with cancer development, establishing them as active contributors to cancer pathology and viable targets for therapeutic intervention. This review advocates for continued research into histone chaperone-targeted therapies, which hold potential for precision medicine in oncology. Future advancements in understanding chaperone functions and interactions are anticipated to lead to novel cancer treatments, enhancing patient care and outcomes. Keywords: histone chaperone; cancer therapy; targeted therapies 1. Introduction DNA stores genetic information. Chromatin, a complex of DNA and proteins, plays a crucial role in organizing and regulating genetic information. Nucleosomes, the basic units of chromatin, each contain 147 base pairs of DNA wrapping around an octamer of histone proteins—two histone H2A/H2B dimers and one histone H3/H4 tetramer [1,2] . These histone proteins provide structural support to compact chromatin structures through DNA condensation [3] . Nucleosomes interacting with histone proteins continue assembly and disassembly by the deposition or eviction of histone proteins, which is modulated by several mechanisms such as ATP-dependent chromatin remodeling, histone post-translational modifications, and the incorporation of histone variants [4,5] . The dynamic nature of chromatin structures allows the fine-tuning of gene expression in response to various cellular signals and environmental impacts. Histone chaperones were first identified in the 1980s and are reported to play a significant role in chromatin dynamics by facilitating nucleosome assembly and disassembly [6] . Unlike other histone-binding proteins, histone chaperones do not exhibit enzymatic activity and act in a histone-specific manner [7] . To date, dozens of histone chaperones have been identified, each with distinct biological functions, including prevention of non-specific interaction with DNA, promotion of their proper deposition/eviction, and trans

FAQs

What roles do histone chaperones play in chromatin biology?

Histone chaperones facilitate nucleosome assembly and disassembly, helping regulate gene expression and maintain genomic stability. They also prevent aberrant histone interactions prior to chromatin assembly.

How is histone chaperone dysregulation linked to cancer?

Dysregulated histone chaperones correlate with cancer development. Changes in expression levels, mutations, or aberrant interactions can disrupt chromatin structure and gene regulation, promoting tumorigenesis and cancer progression.

Why are histone chaperones considered potential therapeutic targets?

Because their dysregulation actively contributes to cancer pathology, histone chaperones represent viable targets for therapeutic intervention. The review emphasizes continued research into chaperone-targeted therapies for precision oncology.

Sep 21, 2026

Uploaded by Maeve