Abstract
Histone H3 phosphorylation is related closely to chromatin remodeling and chromosome condensation. H3 phosphorylation at serine 28 is coupled with mitotic chromosome condensation in diverse mammalian cell lines. However, the pathway that mediates phosphorylation of H3 at serine 28 is unknown. In the present study, ERK1, ERK2, or p38 kinase strongly phosphorylated H3 at serine 28 in vitro. JNK1 or JNK2 was able also to phosphorylate H3 at serine 28 in vitro but to a lesser degree. UVB irradiation markedly induced phosphorylation of H3 at serine 28 in JB6 Cl 41 cells. PD 98059, a MEK1 inhibitor, and SB 202190, a p38 kinase inhibitor, efficiently repressed UVB-induced H3 phosphorylation at serine 28. Expression of dominant negative mutant (DNM) ERK2 in JB6 Cl 41 cells totally blocked UVB-induced phosphorylation of H3 at serine 28. Additionally, DNM p38 kinase or DNM JNK1 partially blocked UVB-induced H3 phosphorylation at serine 28. Furthermore, UVB-induced H3 phosphorylation at serine 28 was inhibited in Jnk1(-/-) cells but not in Jnk2(-/-) cells. These results suggest that UVB-induced H3 phosphorylation at serine 28 may be mediated by mitogen-activated protein kinases.
Highlights
Histones are relatively small proteins with a very high proportion of positively charged amino acids; the positive charge helps the histones bind tightly to DNA regardless of its nucleotide sequence [1]
The results show that pure histone H3 at serine 28 was phosphorylated strongly by ERK1 (Fig. 1A), ERK2 (Fig. 1B), or p38 kinase (Fig. 1C) and to a comparatively lesser degree by JNK1 (Fig. 1D) or JNK2 (Fig. 1E) in vitro
We found that active ERK1, ERK2, and p38 kinase strongly phosphorylated H3 at serine 28, whereas JNK1 and JNK2 phosphorylation of H3 at serine 28 was relatively weaker in vitro
Summary
Histones are relatively small proteins with a very high proportion of positively charged amino acids (lysine and arginine); the positive charge helps the histones bind tightly to DNA regardless of its nucleotide sequence [1]. The phosphorylation of histone H3 is thought to be a highly conserved event among eukaryotes and probably is involved in transcriptional regulation and chromosome condensation during mitosis and meiosis [15, 25, 26]. Previous studies showed that H3 phosphorylation at serine 10 was associated with mitosis in diverse types of eukaryotic cells and with chromosome condensation during mitosis and meiosis [5, 10, 15, 27,28,29]. The pathway responsible for mediating H3 phosphorylation at serine 10 depends on the type of stimulation [25, 26, 32], and phosphorylation of serine 10 in histone H3 is linked functionally in vitro and in vivo to acetylation of histone at lysine 14 [33]. We investigated the role of MAP1 kinases in phosphorylation of H3 at serine 28 in vitro and in vivo after UVB irradiation
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