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Mitotic phosphorylation of MPP8 by cyclin-dependent kinases regulates chromatin dissociation

Makoto Nishigaki1, Yu Kawada, Toshinori Misaki

  • 1Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Nagoya 467-8601, Japan.

Biochemical and Biophysical Research Communications
|February 19, 2013
PubMed

Insights

M phase phosphoprotein 8 (MPP8) dissociates from chromatin during mitosis, regulated by cyclin B1-Cdk1 phosphorylation. This finding clarifies MPP8

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cell Biology

Background:

  • Heterochromatin undergoes significant structural changes during mitosis.
  • Repressive epigenetic marks like DNA methylation and H3K9 methylation are key components of heterochromatin.
  • MPP8 is a proposed regulator of these repressive marks, but its role in mitotic heterochromatin dynamics was unclear.

Purpose of the Study:

  • To investigate the role of MPP8 in the dynamic changes of heterochromatin structure during mitosis.
  • To elucidate the regulatory mechanisms governing MPP8's association with chromatin during the cell cycle.

Main Methods:

  • Immunofluorescence microscopy to track MPP8 localization during interphase and mitosis.
  • Treatment with mitotic kinase inhibitors to identify regulatory pathways.
  • In vitro kinase assays using purified cyclin B1-Cdk1 and MPP8.
  • Analysis of MPP8 mutants with altered phosphorylation sites.

Main Results:

  • MPP8 localizes to chromatin during interphase but dissociates during early mitosis.
  • MPP8 chromatin dissociation is specifically mediated by the cyclin B1-Cdk1 kinase complex.
  • MPP8 phosphorylation by cyclin B1-Cdk1 is essential for its mitotic dissociation from chromatin.
  • A non-phosphorylatable MPP8 mutant (STA mutant) remained bound to chromatin during mitosis.

Conclusions:

  • MPP8's chromatin association is dynamically regulated by Cdk-dependent phosphorylation.
  • Cyclin B1-Cdk1 plays a crucial role in controlling MPP8's mitotic behavior and heterochromatin dynamics.
  • This study reveals a novel mechanism linking cell cycle progression to epigenetic regulation at heterochromatin during mitosis.

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