Specification of the cellular hierarchy in the mammary gland involves complex signaling that remains poorly defined. Polycomb group proteins (PcG) are known to contribute to the specification and maintenance of stem cell identity in multiple tissues through stable alterations in gene expression, yet their importance in the mammary gland remains largely unknown.
Mammalian PcG form two complexes, polycomb repressive complexes 1 and 2 (PRC1 and PRC2), respectively. Polycomb Repressive Complex 2 is composed of at least 3 core components, EED, SUZ12 and the SET-domain containing methyltransferase EZH2, which is overexpressed in human breast cancer. EZH2 catalyzes the formation of a di- or trimethyl mark on lysine 27 of Histone H3 (H3K27), which is recognized and bound by PRC1, leading to transcriptional repression.
We have previously shown that deletion of EZH2 in the mouse mammary epithelium delays mammary gland outgrowth and impairs alveologenesis during pregnancy, but does not lead to overt defects in cell differentiation (1, 2). Consistent with a partially redundant role for EZH2 in the mammary gland, some evidence suggests that a second methyltransferase, EZH1, can partly compensate for EZH2’s function. Unlike EZH2, deletion of the PRC2 core components EED and SUZ12 results in instability of PRC2, suggesting non-redundant roles for these proteins. To investigate the role of PRC2 in mammary epithelium stem and progenitor cell specification, we have conditionally deleted EED and SUZ12 in the mammary gland.