Inhibitor of Differentiation 4 (ID4) represses mammary myoepithelial differentiation via inhibition of HEB
Holly Holliday, Daniel Roden, Simon Junankar, Sunny Z. Wu, Laura A. Baker, Christoph Krisp, Chia‐Ling Chan, Andrea McFarland, Joanna N. Skhinas, Thomas R. Cox, Bhupinder Pal, Nicholas D. Huntington, Christopher J. Ormandy, Jason S. Carroll, Jane E. Visvader, Mark P. Molloy, Alexander Swarbrick
Abstract
. ID4 positively regulates proliferative genes and negatively regulates genes involved in myoepithelial function. Mass spectrometry reveals that ID4 interacts with the bHLH protein HEB, which binds to E-box motifs in regulatory elements of basal developmental genes involved in extracellular matrix and the contractile cytoskeleton. We conclude that high ID4 expression in mammary basal stem cells antagonizes HEB transcriptional activity, preventing myoepithelial differentiation and allowing for appropriate tissue morphogenesis. Downregulation of ID4 during pregnancy modulates gene regulated by HEB, promoting specialization of basal cells into myoepithelial cells.