Protein Synthesis, Post-Translation Modification, and Degradation
Dynamic Changes in Histone H3 Lysine 9 Methylations: IDENTIFICATION OF A MITOSIS-SPECIFIC FUNCTION FOR DYNAMIC METHYLATION IN CHROMOSOME CONGRESSION AND SEGREGATION*

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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.

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*

This work was funded by grants from the Canadian Institutes of Health Research (CIHR) (to M. J. H. and D. A. U.), the Alberta Cancer Board (to M. J. H. and D. A. U.), and the Alberta Heritage Foundation for Medical Research (AHFMR) (to D. A. U.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-3 and Tables 1-3.

1

Recipient of graduate studentships from CIHR and AHFMR.

2

Supported by a postgraduate scholarship from Natural Sciences and Engineering Research Council.

3

An AHFMR Scholar.