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Updated: Nov 18, 2025

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Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer
Talha Anwar1, Maria E Gonzalez2, Celina G Kleer2
1Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Abstract:
Enhancer of Zeste Homologue 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) that is critical for determining cell identity. An epigenetic writer, EZH2 has a well-defined role in transcriptional repression by depositing trimethyl marks on lysine 27 of histone H3. However, there is mounting evidence that histone methyltransferases like EZH2 exert histone methyltransferase-independent functions. The relevance of these functions to breast cancer progression and their regulatory mechanisms are only beginning to become understood. Here, we review the current understanding of EZH2 H3K27me3-independent, noncanonical, functions and their regulation in breast cancer.
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