Interplay between histone H1 structure and function

H1 linker histones are involved both in the maintenance of higher-order chromatin structure and in gene regulation. Histone H1 exists in multiple isoforms, is evolutionarily variable and undergoes a large variety of post-translational modifications. We review recent progress in the understanding of the folding and structure of histone H1 domains with an emphasis on the interactions with DNA. The importance of intrinsic disorder and hydrophobic interactions in the folding and function of the carboxy-terminal domain (CTD) is discussed. The induction of a molten globule-state in the CTD by macromolecular crowding is also considered. The effects of phosphorylation by cyclin-dependent kinases on the structure of the CTD, as well as on chromatin condensation and oligomerization, are described. We also address the extranuclear functions of histone H1, including the interaction with the β-amyloid peptide. This article is part of a Special Issue entitled: Histone H1, edited by Dr. Albert Jordan. •H1 terminal domains are intrinsically disordered regions which fold upon DNA interaction.•Post-translational modifications can modulate H1 structure and function.•Histone H1 can perform extranuclear functions associated with the immune system and with Alzheimer's disease.