Rapid dephosphorylation of H1 histones after apoptosis induction

H1 histones are involved in the formation of higher order chromatin structu res and in the modulation of gene expression. Changes in chromatin structur e are a characteristic initial feature of apoptosis. We therefore have inve stigated the histone H1 pattern of the human leukemic cell line HL60 underg oing programmed cell death, as induced by topoisomerase I inhibition. Histo ne H1 proteins were isolated and analyzed by high performance liquid chroma tography and capillary zone electrophoresis. DNA fragmentation after apopto sis induction was monitored by agarose gel electrophoresis. The patterns of the three H1 histone subtypes extractable from apoptotic HL60 cells signif icantly differed from those of control cells in showing a decrease of phosp horylated H1 subtypes and an increase of the respective dephosphorylated fo rms. This dephosphorylation of H1 histones could be observed already 45 min after apoptosis induction and preceded internucleosomal DNA cleavage by ap proximately 2 h. We conclude that during apoptotic DNA fragmentation, the H 1 histones become rapidly dephosphorylated by a yet unknown protein phospha tase.