Alteration of Histone Modifications for P66Shc Promoter during Cellular Senescence of Human Embryonic Pulmonary Fibroblast Cells

Objective To detect the alterations of histone modifications for P66Shc promoter during cellular replicative senescence and premature senescence induced by hydrogen peroxide(H2O2) of human embryonic lung fibroblasts(HEFs) in vitro.Methods The HEFs were divided into young cells(22 population doubling levels,22PDL),midaged cells(35PDL) and replicative senescent cells(49PDL) and premature senescent cells induced by H2O2(premature senescence,PS) according to the age definition in cell culture.The mRNA level of P66Shc and its histone modifications in the promoter were detected,including acetylation for H3,H4 and methylation for H3(Lys4).Results The mRNA levels of P66Shc of HEFs increased in mid-aged cells,replicative senescence cells and premature senescent cells with significantly statistical difference(P0.05,P0.01) compared with those of young cells.In the promoter(-1 641-1 392 bp) of P66Shc IP1,the main histone modification was H4 alteration for both mid-aged and replicative senescent cells,while H3,H4 acetylation and H3Lys4 methylation jointly for premature senescent cells.In the region(-129-+45 bp) of IP2,the main histone modification was H3 Lys4 methylation for both mid-aged and replicative senescent cells,while H4 acetylation and H3Lys4 methylation combinedly for premature senescent cells.Conclusion The histone modifications in the promoter region take part in regulating the mRNA expression for P66Shc during cellular senescence and different mechanisms exist between replicative and premature senescence.