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

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

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Epigenetic Factors in Normal and Malignant Hematopoiesis, Aix Marseille Université, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, 13273 Marseille Cedex 9, France.
Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, 34293 Montpellier, Cedex 5, France.
Gustave Roussy, Université Paris-Saclay, Inserm U1170, CNRS Villejuif, France.
Aix Marseille Université, CNRS, IBDM, UMR 7288, 13288 Marseille, Cedex 9, France.


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.

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