Linker histones as liquid-like glue for chromatin

Abstract

Linker histones play essential roles in chromatin structure and function by binding to nucleosomes and modulating the accessibility of DNA for biological processes such as gene transcription and DNA replication (reviewed in ref. 1). For example, DNA promoters of actively transcribed genes and DNA undergoing replication both exhibit reduced linker histone binding (2⇓–4). However, although the structure of the nucleosome core particle was reported in 1997 (5), insights into the structure and function of linker histones within chromatin have emerged only recently (1). Linker histones are small proteins with an ∼75-residue globular domain flanked by N- and C-terminal intrinsically disordered regions (IDRs; between ∼20 and ∼100 residues and ∼100 residues, respectively). The folded domain binds core and linker DNA on (6) or near (7) the nucleosome dyad symmetry axis (6). While the N-terminal IDR plays only a minor role, the C-terminal IDR [termed C-terminal domain (CTD) hereafter], composed of ∼40% lysine residues, contributes significantly to nucleosome condensation by linker histones (8, 9) and dramatically enhances nucleosome binding (>1,000-fold increased affinity) (10). Due to their intrinsic disorder, the CTDs are usually not resolved in X-ray crystallography and cryo-electron microscopy (cryo-EM) data for nucleosomes containing linker histones. A recent cryo-EM study of histone H1 bound to nucleosomes (11) revealed that density for the CTD preferentially associated with one of the two linker DNA segments; however, relatively low resolution (∼10 A) precluded detailed structural analysis of this density. Thus, while the structure and nucleosome-positioning role of the globular domain of linker histones are known, the structural details of CTD–linker DNA interactions have remained elusive. In PNAS, Turner et al. (12) report that the CTD of chicken histone H1.11L (termed CH1) remains disordered and dynamic upon binding to short double-stranded DNA (dsDNA) oligonucleotides and that, upon reaching a critical stoichiometry … [↵][1]1To whom correspondence should be addressed. Email: richard.kriwacki{at}stjude.org. [1]: #xref-corresp-1-1