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.