Multifunctionality of the linker histones: an emerging role for protein-protein interactions

Abstract

Linker histones, e.g., H1, are best known for their ability to bind to nucleosomes and stabilize both nucleosome structure and condensed higher-order chromatin structures. However, over the years many investigators have reported specific interactions between linker histones and proteins involved in important cellular processes. The purpose of this review is to highlight evidence indicating an important alternative mode of action for H1, namely protein-protein interactions. We first review key aspects of the traditional view of linker histone action, including the importance of the H1 C-terminal domain. We then discuss the current state of knowledge of linker histone interactions with other proteins, and, where possible, highlight the mechanism of linker histone-mediated protein-protein interactions. Taken together, the data suggest a combinatorial role for the linker histones, functioning both as primary chromatin architectural proteins and simultaneously as recruitment hubs for proteins involved in accessing and modifying the chromatin fiber.

Figure 1

The linker histone, particularly the long CTD, has the potential to mediate multiple, simultaneous interactions when bound to the nucleosome. Ribbon diagrams of the 3D structures of Xenopus laevis core histone H2B (A) and Gallus gallus linker histone H1 (B). Models for histones H2B and H1 were derived from PDB entries 1AOI [1] and the first model from entry 1GHC [121], respectively. The histone tails were constructed in Coot [122] by making virtual concatamers of the H2B NTD residues visible in the X-ray structure. Images were made with the program VMD [123]. Every effort was made to ensure the C- and N-terminal extensions were created to scale, approximately 3.5 Ǻ per residue for an extended peptide devoid of secondary structure.