Histone deacetylase inhibitors induce apoptosis in peripheral blood lymphocytes along with histone H4 acetylation and the expression of the linker histone variant, H1 degrees.

The results of this study show that H1 degrees can be induced by sodium butyrate and trichostatin A in peripheral blood lymphocytes, a cell system which does not normally express this linker histone variant. Moreover, this induced expression was found to be correlated in a dose-dependent manner with the concomitant induction of apoptosis and increased levels of histone H4 acetylation. Sodium butyrate and trichostatin A, both inhibitors of histone deacetylases, are known to induce terminal differentiation and at the same time the induction of the linker histone variant, H1 degrees, in a number of tissue/cell systems.

mRNA levels of the differentiation-associated linker histone variant H1 zero in mitotically active and postmitotic senescent human diploid fibroblast cell populations.

The mRNA levels of the linker histone variant H1o, which is tightly associated with differentiation, have been studied in the present investigation in an in vitro model ageing human diploid fibroblast (HDF) cell system as a function of cumulative population doublings (CPDs) in mitotically active and senescent cell populations. According to our previous findings the synthesis rate of the H1o protein does not change as a function of CPDs as long as the cells are proliferating. However, when cells reach senescence, the synthesis rate of H1o increases in both naturally aged as well as in cell populations artificially aged by treatment with sodium butyrate.

mRNA levels of the linker histone variant, H1o, in mitotically active human diploid fibroblasts as a function of the phases of the cell cycle and cumulative population doublings.

Senescence and differentiation have many similarities with respect to certain aspects of gene expression and cell cycle related events. One linker histone variant tightly associated with differentiation is the H1 variant, H1o. The work of this investigation has focused on the expression of H1o during the phases of the cell cycle and as a function of increasing cumulative population doublings (CPD) in an in vitro model ageing cell system, namely, human diploid fibroblasts.

T-lymphocyte long-term cultures have a constant histone variant pattern during aging.

Human peripheral long-term T-lymphocyte cell cultures show some characteristics similar to those of fibroblast cell lines, the latter of which have been used as in vitro systems for cellular aging studies for many years. Both show a limited in vitro life span, as well as a progressive prolongation of their cell cycle with increasing age. However, whereas T-cell cultures die from apoptosis at the end of their proliferative capacity, fibroblasts can be maintained for long periods of time in stationary cultures as postmitotic senescent cells.