PAX3 loads onto pericentromeric heterochromatin during S phase through PARP1

Anticancer Res. 2014 Sep;34(9):4717-22.

Abstract

Background: Proper re-establishment of heterochromatin after each round of DNA replication is critical to the preservation of cell identity. Paired box 3 (PAX3), a transcription factor important in embryonic development, was found to mediate the formation of pericentromeric heterochromatin. However, how PAX3 recognizes the heterochromatic environment and re-establishes it after DNA replication remains unclear.

Materials and methods: Cell-cycle synchronization, fluorescence microscopic analyses, and co-immunoprecipitation were used to analyze the heterochromatic localization of PAX3 in HEK 293 cells and NIH 3T3 cells.

Results: We found that PAX3 binds pericentromeric heterochromatin during middle-to-late S phase. Loading of PAX3 onto pericentromeric heterochromatin requires poly(ADP-ribose) polymerase 1 (PARP1). Furthermore, loss of PAX3 or PARP1 delays cell-cycle progression through the S phase.

Conclusion: Our results reveal how PAX3 recognizes and maintains pericentromeric heterochromatin at the S phase of the cell cycle.

Keywords: PARP1; PAX3; S phase; pericentromeric heterochromatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • HEK293 Cells
  • Heterochromatin / genetics
  • Heterochromatin / metabolism*
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Protein Binding
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism
  • S Phase*

Substances

  • Heterochromatin
  • Paired Box Transcription Factors
  • Recombinant Fusion Proteins
  • Poly(ADP-ribose) Polymerases