Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes
- Judd C. Rice1,4,
- Kenichi Nishioka2,4,
- Kavitha Sarma2,
- Ruth Steward3,
- Danny Reinberg2, and
- C. David Allis1,5
- 1Department of Biochemistry & Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia 22908-0733, USA; 2Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA; 3Waksman Institute, Department of Molecular Biology & Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA
Abstract
We describe distinct patterns of histone methylation during human cell cycle progression. Histone H4 methyltransferase activity was found to be cell cycle-regulated, consistent with increased H4 Lys 20 methylation at mitosis. This increase closely followed the cell cycle-regulated expression of the H4 Lys 20 methyltransferase, PR-Set7. Localization of PR-Set7 to mitotic chromosomes and subsequent increase in H4 Lys 20 methylation were inversely correlated to transient H4 Lys 16 acetylation in early S-phase. These data suggest that H4 Lys 20 methylation by PR-Set7 during mitosis acts to antagonize H4 Lys 16 acetylation and to establish a mechanism by which this mark is epigenetically transmitted.
