Histone H1 Subtypes Differentially Modulate Chromatin Condensation without Preventing ATP-Dependent Remodeling by SWI/SNF or NURF

Abstract

Although ubiquitously present in chromatin, the function of the linker histone subtypes is partly unknown and contradictory studies on their properties have been published. To explore whether the various H1 subtypes have a differential role in the organization and dynamics of chromatin we have incorporated all of the somatic human H1 subtypes into minichromosomes and compared their influence on nucleosome spacing, chromatin compaction and ATP-dependent remodeling. H1 subtypes exhibit different affinities for chromatin and different abilities to promote chromatin condensation, as studied with the Atomic Force Microscope. According to this criterion, H1 subtypes can be classified as weak condensers (H1.1 and H1.2), intermediate condensers (H1.3) and strong condensers (H1.0, H1.4, H1.5 and H1x). The variable C-terminal domain is required for nucleosome spacing by H1.4 and is likely responsible for the chromatin condensation properties of the various subtypes, as shown using chimeras between H1.4 and H1.2. In contrast to previous reports with isolated nucleosomes or linear nucleosomal arrays, linker histones at a ratio of one per nucleosome do not preclude remodeling of minichromosomes by yeast SWI/SNF or Drosophila NURF. We hypothesize that the linker histone subtypes are differential organizers of chromatin, rather than general repressors.

Nucleosome Interaction Surface of Linker Histone H1c Is Distinct from That of H10

“…Most studies addressing linker histone heterogeneity have focused on quantitative assessment of the binding affinity or chromatin condensing abilities of the various subtypes and conclude that the highly divergent C terminus is the primary domain responsible for these differences (24,26,37,42). Here, we show, utilizing in vivo photobleaching of unperturbed chromatin, that there are qualitative differences in the binding surfaces of the conserved globular domains of two somatic H1 variants.…”

Quantitative Proteomics Reveals a Role for Epigenetic Reprogramming During Human Monocyte Differentiation

“…S5). The linker histone proteins H1s define chromatin structures and are normally considered to be chromatin repressors (1,55). Chromatin in monocytes was associated with highly expressed H1s and differed from chromatin in dendritic cells, which was associated with low levels of histone H1 expression.…”

N- and C-terminal Domains Determine Differential Nucleosomal Binding Geometry and Affinity of Linker Histone Isotypes H10 and H1c

“…H1 isotypes isolated from rat brains were classified as possessing high (H1e, H1 0 , and H1d), intermediate (H1c and H1b), and low binding affinities (H1a) (38). No appreciable differences in the binding affinities between human H1 isotypes H1-0 and H1.2 (the paralog of mouse H1c) were found in in vitro assays (39), although these isotypes were reported to have different binding characteristics by in vivo experiments (40). 50 ) were determined as previously described (35) and represent the means Ϯ S.D.…”