From Happel et al., a detailed characterization of histone H1 profiles in peripheral blood lymphocytes over the course of aging. The authors demonstrate significant differences in post-translational modifications of several histone H1 isoforms, and conclude that these changes may be implicated in age-related chromatin remodeling:
H1 histone subtype constitution and phosphorylation state of the ageing cell system of human peripheral blood lymphocytes
Until a few years ago, the H1 histones were exclusively considered to be the architectural proteins of chromatin involved in chromatin condensation. However there is now increasing data to support the hypothesis that the H1 subtypes are involved in genomic integrity and that they may have unexpected functional roles in various biological processes such as in differentiation and DNA repair, apoptosis and lifespan. Moreover, the H1 histones are phosphorylated to a great extent. Recent work has implicated phosphorylation of H1 in the regulation of chromatin remodeling. In light of the fact that chromatin reorganization and heterochromatin formation has been shown to take place during ageing and senescence, in the present investigation, we have analyzed the changes that take place in the somatic H1 linker histone subtype profile and their phosphorylation states in human peripheral blood lymphocytes as a function of donor age. Results from this work show that there is a significant age-related dephosphorylation of H1.4 and H1.5 and an increase in the heterochromatin protein HP1α as a function of donor age. These results indicate that dephosphorylation of H1 histones may be related to an increase in senescence-associated heterochromatin formation during the in vivo ageing of human peripheral blood lymphocytes.
The specific situation in immune cells appears to be quite different from the case in fibroblasts, where histone H1 is completely lost at senescence. In both cases, however, the change in histone H1 profile is tightly associated with the form of chromatin modeling termed Senescence-Associated Heterochromatic Foci (SAHFs).