Dynamic changes in histone H3 lysine 9 methylations: identification of a mitosis-specific function for dynamic methylation in chromosome congression and segregation.
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.
McManus
Kirk J
KJ
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada.
Biron
Vincent L
VL
Heit
Ryan
R
Underhill
D Alan
DA
Hendzel
Michael J
MJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002461:Cell Line, Transformed; D020090:Chromosome Segregation; D002877:Chromosomes, Human; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007211:Indoles; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry*; D008745:Methylation; D008938:Mitosis; D018668:Muntjacs; D015739:Nocodazole / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D006657:Histones; D007211:Indoles; D020033:Protein Isoforms; D049452:Green Fluorescent Proteins; C027579:periodate-oxidized adenosine; C007293:DAPI; D008239:Lysine; D000241:Adenosine; D015739:Nocodazole