MAP kinases mediate WE-induced phosphorylation of histone H3 at serine 28

Histone H3 phosphorylation is related closely to chromatin remodeling and c hromosome condensation. H3 phosphorylation at serine 28 is coupled with mit otic 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 ser ine 28 in vitro. JNK1 or JNK2 was able also to phosphorylate H3 at serine 2 8 in vitro but to a lesser degree. UVB irradiation markedly induced phospho rylation of H3 at serine 28 in JB6 Cl 41 cells. PD 98059, a MEK1 inhibitor, and SE 202190, a p38 kinase inhibitor, efficiently repressed UVB-induced H 3 phosphorylation at serine 28, Expression of dominant negative mutant DNM ERK2 in JB6 Cl 41 cells totally blocked UVB-induced phosphorylation of H3 a t serine 28. Additionally, DNM p38 kinase or DNM JNK1 partially blocked UVB -induced H3 phosphorylation at serine 28, Furthermore, UVB-induced H3 phosp horylation at serine 28 was inhibited in Jnk1(-/-) cells but not in Jnk2(-/ -) cells. These results suggest that UVB-induced H3 phosphorylation at seri ne 28 may be mediated by mitogen-activated protein kinases.