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Augmentation of Myc-Dependent Mitotic Gene Expression by the Pygopus2 Chromatin Effector

Phillip G P Andrews1, Catherine Popadiuk2, Thomas J Belbin3

  • 1Terry Fox Cancer Research Labs, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's Campus, NL A1B 3V6, Canada.

Cell Reports
|May 3, 2018
PubMed

Insights

Pygopus (Pygo)2 is essential for MYC-dependent gene expression, controlling cancer cell division. Its depletion causes mitotic arrest by disrupting chromosome-spindle interactions crucial for cell replication.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Accurate chromosome segregation during mitosis is vital for cell division.
  • Transcriptional control mechanisms for genes involved in mitosis are not fully understood.

Purpose of the Study:

  • To investigate the role of the chromatin effector Pygopus (Pygo)2 in regulating MYC-dependent genes essential for cell division.
  • To elucidate the mechanism by which Pygo2 influences chromosomal segregation and mitosis.

Main Methods:

  • Depletion of Pygo2 in SKOV-3 cells.
  • Chromatin immunoprecipitation and global chromatin association studies in HeLa S3 cells.
  • Immunoprecipitation and proximity ligation assays.
  • Analysis of a MYC-driven prostate cancer model.

Main Results:

  • Pygo2 depletion led to metaphase arrest due to failed chromosome capture of spindle microtubules.
  • Pygo2 and MYC were enriched at promoters of genes involved in chromosomal biorientation and segregation.
  • Pygo2 maintained histone H3K27 acetylation at these gene promoters.
  • MYC and Pygo2 physically interact within the nucleus.

Conclusions:

  • Pygopus (Pygo)2 is indispensable for the expression of MYC-dependent genes regulating cancer cell division.
  • Pygo2 plays a critical role in ensuring proper chromosomal biorientation and segregation during mitosis.
  • Pygo2 is an essential component of MYC's oncogenic activity in mitosis.
Keywords:
PygopusWntmitosismyconcogeneprostate cancer

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