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Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo.

The mammalian Polycomblike protein PHF1 was previously shown to interact with the Polycomb group (PcG) protein Ezh2, a histone methyltransferase whose activity is pivotal in sustaining gene repression during development and in adulthood. As Ezh2 is active only when part of the Polycomb Repressive Complexes (PRC2-PRC4), we examined the functional role of its interaction with PHF1. Chromatin immunoprecipitation experiments revealed that PHF1 resides along with Ezh2 at Ezh2-regulated genes such as the HoxA loci and the non-Hox MYT1 and WNT1 genes. Knockdown of PHF1 or of Ezh2 led to up-regulated HoxA gene expression. Interestingly, depletion of PHF1 did correlate with reduced occupancy of Bmi-1, a PRC1 component. As expected, knockdown of Ezh2 led to reduced levels of its catalytic products H3K27me2/H3K27me3. However, reduced levels of PHF1 also led to decreased global levels of H3K27me3. Notably, the levels of H3K27me3 decreased while those of H3K27me2 increased at the up-regulated HoxA loci tested. Consistent with this, the addition of PHF1 specifically stimulated the ability of Ezh2 to catalyze H3K27me3 but not H3K27me1/H3K27me2 in vitro. We conclude that PHF1 modulates the activity of Ezh2 in favor of the repressive H3K27me3 mark. Thus, we propose that PHF1 is a determinant in PcG-mediated gene repression.

Pubmed ID: 18285464


  • Sarma K
  • Margueron R
  • Ivanov A
  • Pirrotta V
  • Reinberg D


Molecular and cellular biology

Publication Data

April 27, 2008

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM64844
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Catalysis
  • Cell Line
  • Cell Proliferation
  • Cell Shape
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Humans
  • Lysine
  • Methylation
  • Polycomb Repressive Complex 2
  • Polycomb-Group Proteins
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Small Interfering
  • Repressor Proteins
  • Transcription Factors
  • Transcription, Genetic