During this reporting period the Laboratory of Genetics and Physiology has continued and expanded a program aimed at exploring the interphase between cytokine-STAT5 signaling and epigenetic programming of cells. In particular we have addressed the question whether the ability of the transcription factor STAT5 to differentially activate genetic programs in distinct cell types and during specific developmental windows is influenced by the concentration of STAT5. In order to answer this question, we have generated mouse embryonic fibroblasts (MEFs) carrying three different genotypes, wild type MEFs, STAT5-null MEFs and MEFs containing 10-fold higher STAT5 concentrations than wild type MEFs. Using these MEFs containing different concentrations of STAT5 we performed ChIP-seq experiments to identify genome-wide the entire set of loci that interact with STAT5. Moreover, we performed corresponding gene expression analyses. LGP is currently working with computational biologists from KAIST and POSTECH (South Korea) to analyze these large data sets. In an extension of this program, LGP scientists have initiated mouse genetic experiments aimed at addressing the question whether the epigenetic landscape in mammary epithelium undergoes changes during pregnancy and whether this relates to the activation of developmental programs aimed at controlling cell proliferation and differentiation.
