The enhancement of histone H4 and H2A serine 1 phosphorylation during mitosis and S-phase is evolutionarily conserved.
Histone phosphorylation has long been associated with condensed mitotic chromatin; however, the functional roles of these modifications are not yet understood. Histones H1 and H3 are highly phosphorylated from late G2 through telophase in many organisms, and have been implicated in chromatin condensation and sister chromatid segregation. However, mutational analyses in yeast and biochemical experiments with Xenopus extracts have demonstrated that phosphorylation of H1 and H3 is not essential for such processes. In this study, we investigated additional histone phosphorylation events that may have redundant functions to H1 and H3 phosphorylation during mitosis. We developed an antibody to H4 and H2A that are phosphorylated at their respective serine 1 (S1) residues and found that H4S1/H2AS1 are highly phosphorylated in the mitotic chromatin of worm, fly, and mammals. Mitotic H4/H2A phosphorylation has similar timing and localization as H3 phosphorylation, and closely correlates with the chromatin condensation events during mitosis. We also detected a lower level of H4/H2A phosphorylation in 5-bromo-2-deoxyuridine-positive S-phase cells, which corroborates earlier studies that identified H4S1 phosphorylation on newly synthesized histones during S-phase. The evolutionarily conserved phosphorylation of H4/H2A during the cell cycle suggests that they may have a dual purpose in chromatin condensation during mitosis and histone deposition during S-phase.
Barber
Cynthia M
CM
Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, VA 22908, USA.
Turner
Fiona B
FB
Wang
Yanming
Y
Hagstrom
Kirsten
K
Taverna
Sean D
SD
Mollah
Sahana
S
Ueberheide
Beatrix
B
Meyer
Barbara J
BJ
Hunt
Donald F
DF
Cheung
Peter
P
Allis
C David
CD
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006367:HeLa Cells; D006657:Histones / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007399:Interphase; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
D000906:Antibodies; D002843:Chromatin; D006657:Histones; D012694:Serine