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Linker Histones: The Multiple Binding Modes of the Enigmatic 5th Histone

Aug 2026 · Biomolecules · Vol 16, pp. 1181 · 0 citations · 92 references
Medicine

TL;DR

This review introduces the basics of chromatin structure, what is known about how linker histones (H1s) bind to nucleosomes and influence chromatin, and how the individual domains within H1s contribute to these activities.

Abstract

Chromatin structure is dynamic and regulated by many factors, including enzymes that chemically modify histones and DNA, chromatin remodeling complexes that physically manipulate nucleosomes and chromatin, and non-enzymatic proteins that bind to DNA or nucleosomes to create specialized regions in chromatin. This multifactorial regulation stems from the need for fine-tuned control, which is key in processes including DNA repair, replication, and gene expression. Linker histones are a family of proteins structurally distinct from the core histones that provide a poorly understood layer of regulation in chromatin. In this review, we introduce the basics of chromatin structure, what is known about how linker histones (H1s) bind to nucleosomes and influence chromatin, and how the individual domains within H1s contribute to these activities. We especially focus on recent studies describing canonical and alternative H1-nucleosome binding and their potential roles in chromatin.

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