Rapid dephosphorylation of H1 histones after apoptosis induction.
H1 histones are involved in the formation of higher order chromatin structures and in the modulation of gene expression. Changes in chromatin structure are a characteristic initial feature of apoptosis. We therefore have investigated the histone H1 pattern of the human leukemic cell line HL60 undergoing programmed cell death, as induced by topoisomerase I inhibition. Histone H1 proteins were isolated and analyzed by high performance liquid chromatography and capillary zone electrophoresis. DNA fragmentation after apoptosis induction was monitored by agarose gel electrophoresis. The patterns of the three H1 histone subtypes extractable from apoptotic HL60 cells significantly differed from those of control cells in showing a decrease of phosphorylated H1 subtypes and an increase of the respective dephosphorylated forms. This dephosphorylation of H1 histones could be observed already 45 min after apoptosis induction and preceded internucleosomal DNA cleavage by approximately 2 h. We conclude that during apoptotic DNA fragmentation, the H1 histones become rapidly dephosphorylated by a yet unknown protein phosphatase.
Kratzmeier
M
M
Institute for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Albig
W
W
Hanecke
K
K
Doenecke
D
D
D017209:Apoptosis; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D018922:HL-60 Cells; D006657:Histones / Q000145:classification / Q000378:metabolism*; D006801:Humans; D008387:Marine Toxins; D009707:Nucleosomes / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019772:Topotecan / Q000494:pharmacology
D004273:DNA, Neoplasm; D006657:Histones; D008387:Marine Toxins; D009707:Nucleosomes; D010080:Oxazoles; C059041:calyculin A; D019772:Topotecan; D011493:Protein Kinase C; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate