Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer

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.