Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity

Nucleic Acids Res. 2018 Apr 20;46(7):3339-3350. doi: 10.1093/nar/gky080.

Abstract

The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level. We find that co-occupancy of PLZF and EZH2 on chromatin at PLZF target genes is not associated with SUZ12 or trimethylated lysine 27 of histone H3 (H3K27me3) but with the active histone mark H3K4me3 and active transcription. Removal of EZH2 leads to an increase of PLZF binding and increased gene expression. Our results suggest a new role of EZH2 in restricting PLZF positive transcriptional activity independently of its canonical PRC2 activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Self Renewal / genetics
  • Chromatin / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Gene Expression Regulation / genetics
  • Hematopoietic Stem Cells / metabolism
  • Histone Methyltransferases / genetics
  • Histones / genetics
  • Humans
  • Neoplasm Proteins
  • Polycomb Repressive Complex 2 / genetics*
  • Promyelocytic Leukemia Zinc Finger Protein / genetics*
  • Protein Binding / genetics
  • Transcription Factors
  • Transcription, Genetic*

Substances

  • Chromatin
  • Histones
  • Neoplasm Proteins
  • Promyelocytic Leukemia Zinc Finger Protein
  • SUZ12 protein, human
  • Transcription Factors
  • histone H3 trimethyl Lys4
  • ZBTB16 protein, human
  • Histone Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2