Chromatin effector Pygo2 mediates Wnt-notch crosstalk to suppress luminal/alveolar potential of mammary stem and basal cells.

ABSTRACT: Epigenetic mechanisms regulating lineage differentiation of mammary stem cells (MaSCs) remain poorly understood. Pygopus 2 (Pygo2) is a histone methylation reader and a context-dependent Wnt/β-catenin coactivator. Here we provide evidence for Pygo2's function in suppressing luminal/alveolar differentiation of MaSC-enriched basal cells. We show that Pygo2-deficient MaSC/basal cells exhibit partial molecular resemblance to luminal cells, such as elevated Notch signaling and reduced mammary repopulating capability upon transplantation. Inhibition of Notch signaling suppresses basal-level and Pygo2-deficiency-induced luminal/alveolar differentiation of MaSC/basal cells, whereas activation of Wnt/β-catenin signaling suppresses luminal/alveolar differentiation and Notch3 expression in a Pygo2-de

SUBMITTER: Gu B 

PROVIDER: S-EPMC3703489 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature