Cell Senescence Is Associated With Decreased Biotinylation Of Histone H4 In Imr90 Human Fibroblasts

Primary human cells undergo a limited number of cell divisions before entering senescence. Shortening of heterochromatic repeats in telomeres at chromosome ends is a critical event in cell senescence. In previous studies we provided evidence that biotinylated histone are greatly enriched in heterochromatin. Here we tested the hypothesis that shortening of telomeres in aging human cells is associated with depletion of biotinylated histone H4 in chromatin. Human IMR90 lung fibroblasts were cultured for a period of time spanning population doublings (PD) 26 to 40 and samples were collected at timed intervals; activity of beta-galactosidase correlated with PD, consistent with cell aging. The abundance of biotinylated histone H4 was about 50% lower at PD 40 compared with PD 26. If telomere attrition was prevented by overexpression of human telomerase, the abundance of biotinylated histone H4 did not depend on PD; and no signs of senescence were detected. These observations are consistence with the notion that biotinylated histone H4 might play a role in telomere structures and cell senescence. Supported by NIH grants DK 60447 and DK 063945, and NSF EPSCoR grant 0346476.