Mitsui Y, Sakagami H, Yamada M
Adv Exp Med Biol. 1985;190:373-89. doi: 10.1007/978-1-4684-7853-2_19.
Histone H1 content and synthesis were examined in normal, Werner-syndrome, and transformed fibroblasts. Analysis of 3H-lysine incorporation indicated that senescent cells, but not G1-arrested young cells, had a lower ratio of molar synthesis of H1 histone to nucleosome histones than did growing young cells or gamma-ray-transformed cells. Furthermore, a biochemical study of histone H1 content plotted as a function of DNA synthesis activity and an immunocytological study using antiserum against histone H1 revealed that senescent cells had a lower histone H1 content than did young cultures at all stages of cell proliferation. Werner syndrome skin fibroblasts at early passage, however, had amounts of histone H1 comparable to those of age-matched normal control fibroblasts. We conclude that a decline, with increasing passage number, in content and synthesis of H1 histone relative to nucleosomal histones (Mitsui et al., 1980) was not simply due to passage-related accumulation of G1-arrested cells, but actually reflected age specific changes of cultured human fibroblasts. The depletion of histone H1 in the chromatin of senescent cells is a possible cause of DNA strand breakage or relaxation of gene repression.
在正常、沃纳综合征和转化的成纤维细胞中检测了组蛋白H1的含量和合成情况。对³H-赖氨酸掺入的分析表明，衰老细胞而非处于G1期阻滞的年轻细胞，与生长中的年轻细胞或γ射线转化细胞相比，H1组蛋白与核小体组蛋白的摩尔合成比率较低。此外，一项将组蛋白H1含量作为DNA合成活性函数的生化研究以及一项使用抗组蛋白H1抗血清的免疫细胞研究表明，在细胞增殖的所有阶段，衰老细胞的组蛋白H1含量均低于年轻培养物。然而，早期传代的沃纳综合征皮肤成纤维细胞的组蛋白H1含量与年龄匹配的正常对照成纤维细胞相当。我们得出结论，相对于核小体组蛋白，H1组蛋白的含量和合成随传代次数增加而下降（Mitsui等人，1980年），这并非仅仅是由于与传代相关的G1期阻滞细胞的积累，而是实际上反映了培养的人成纤维细胞的年龄特异性变化。衰老细胞染色质中组蛋白H1的消耗可能是DNA链断裂或基因抑制松弛的原因。
