Peroxisome proliferator-activated receptor γ controls Muc1 transcription in trophoblasts

The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is essential for placental development. Here, we show that the mucin gene Muc1 is a PPARγ target, whose expression is lost in PPARγ null placentas. During differentiation of trophoblast stem cells, PARγ is strongly induced, and Muc1 expression is upregulated by the PPARγ agonist rosiglitazone. Muc1 promoter is activated strongly and specifically by liganded PPARγ but not PPARα or PPARδ. A PPAR binding site (DR1) in the proximal Muc1 promoter acts as a basal silencer in the absence of PPARγ, and its cooperation with a composite upstream enhancer element is both necessary and sufficient for PPARγ-dependent induction of Muc1. In the placenta, MUC1 protein is localized exclusively to the apical surface of the labyrinthine trophoblast around maternal blood sinuses, resembling its luminal localization on secretory epithelia. Last, variably penetrant maternal blood sinus dilation in Muc1-deficient placentas suggests that Muc1 regulation by PPARγ contributes to normal placental development but also that the essential functions of PPARγ in the organ are mediated by other targets.