Dynamic Changes in Histone H3 Lysine 9 Methylations
IDENTIFICATION OF A MITOSIS-SPECIFIC FUNCTION FOR DYNAMIC METHYLATION IN CHROMOSOME CONGRESSION AND SEGREGATION*
- Kirk J. McManus‡,1,
- Vincent L. Biron§,2,
- Ryan Heit‡,
- D. Alan Underhill§,3 and
- Michael J. Hendzel‡,3,4
- ‡Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada and the §Department of Medical Genetics, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
- ↵4 To whom correspondence should be addressed: Dept. of Oncology, Cross Cancer Institute, 11560 University Ave., Rm. 3332, Edmonton, Alberta T6G 1Z2, Canada. Tel.: 780-432-8493; Fax: 780-432-8892; E-mail: michaelh{at}cancerboard.ab.ca.
Abstract
Histone methylation is unique among post-translational histone modifications by virtue of its stability. It is thought to be a relatively stable and heritable epigenetic mark for gene-specific regulation. In this study, we use quantitative in situ approaches to investigate the cell cycle dynamics of methylated isoforms of histone H3 lysine 9. Contrary to the expected stability of trimethylated lysines, our results for trimethylated lysine 9 (tMeK9) of H3 demonstrate that the genomic content of this methylation undergoes significant changes as cells progress through mitosis. Unexpectedly, there is a loss of tMeK9 that appears to reflect a robust demethylase activity that is active during the period between anaphase and cytokinesis. Subsequent investigations of mitoses in tMeK9-deficient cells revealed defects in chromosome congression and segregation that are distinct from the increased cohesion at centromeres previously reported in association with the loss of tMeK9. Collectively, these results identify a mitosis-specific trimethylation of Lys9 in pericentromeric heterochromatin that functions in the faithful segregation of chromosomes.
- Received May 16, 2005.
- Revision received December 21, 2005.
- The American Society for Biochemistry and Molecular Biology, Inc.
