The role of linker histone H1 modifications in the regulation of gene expression and chromatin dynamics

Abstract

Background: Linker histone H1 is a structural component of chromatin. It exists as a family of related proteins known as variants and/or subtypes. H1.1, H1.2, H1.3, H1.4 and H1.5 are present in most somatic cells, whereas other subtypes are mainly expressed in more specialized cells.

Scope of review: H1 subtypes have been shown to have unique functions in chromatin structure and dynamics. This can occur at least in part via specific post-translational modifications of distinct H1 subtypes. However, while core histone modifications have been extensively studied, our knowledge of H1 modifications and their molecular functions has remained for a long time limited to phosphorylation. In this review we discuss the current state of knowledge of linker histone H1 modifications and where possible highlight functional differences in the modifications of distinct H1 subtypes.

Major conclusions and general significance: H1 histones are intensely post-translationally modified. These modifications are located in the N- and C-terminal tails as well as within the globular domain. Recently, advanced mass spectrometrical analysis revealed a large number of novel histone H1 subtype specific modification sites and types. H1 modifications include phosphorylation, acetylation, methylation, ubiquitination, and ADP ribosylation. They are involved in the regulation of all aspects of linker histone functions, however their mechanism of action is often only poorly understood. Therefore systematic functional characterization of H1 modifications will be necessary in order to better understand their role in gene regulation as well as in higher-order chromatin structure and dynamics.

Keywords: Chromatin dynamics; Epigenetic; H1 subtypes; Linker histone H1.