Meeting Abstract

26.11  Monday, Jan. 5  Evolution of physical interactions among the transcription factors HoxA-11 and FOXO1a during the evolution of pregnancy in mammals. BRAYER, K.J.*; LYNCH, V.J.; WAGNER, G.P.; Yale University, New Haven; Yale University, New Haven; Yale University, New Haven kathryn.brayer@yale.edu

Decidualization of endometrial stromal cells is a critical step in the successful establishment of pregnancy. Although the molecular mechanisms that regulate decidualization are poorly understood, the importance of elevated levels of prolactin, which are maintained throughout pregnancy, has long been recognized. Endometrial prolactin expression is a derived character of eutherian mammals and is regulated by a tissue specific promoter comprised of two transposable elements, MER20 and MER39, located upstream of the transcription start site. MER20 contains binding sites for numerous transcription factors, including HoxA-11 and FOXO1A. Recently we demonstrated a phylogenetically derived functional interaction between these two proteins resulting in upregulation of expression from the MER20 promoter. Here we examine physical interactions between ancestral and derived HoxA-11, FOXO1A and MER20. Specifically we want to test whether the derived functional interaction involves novel or stronger binding affinity among the molecules or whether it also includes a derived transcriptional activity by the transcription factor proteins. Implications for the evolution of prolactin regulation will be discussed.