Developmentally regulated expression of the transcription factor PRDM1 in the mouse

The master transcriptional regulator Blimp-1/PRDM1 contains an N-terminal PR/SET domain and five C2H2 zinc fingers located near its C-terminus that mediate DNA binding, nuclear import, and recruitment of histone modifying enzymes. These activities account for its ability to control cell-fate decisions and govern tissue homeostasis in multiple cell types in the developing embryo and adult organism (reviewed Bikoff et al., 2009).
In the early embryo Blimp-1/PRDM1 silences the default somatic pathway and causes a few epiblast cells to become exclusively allocated to the germ cell lineage. Blimp-1/PRDM1 also regulates placental and forelimb development, pharyngeal and heart morphogenesis, adult skin homeostasis, and governs postnatal re-programming of intestinal enterocytes (Robertson et al, 2007; Morgan et al., 2009; Harper et al., 2010, Mould et al., 2012, 2015). Blimp-1/PRDM1 associations with numerous epigenetic partners potentially mediate gene silencing and re-organize chromatin structure at cell type-specific target sites (reviewed Bikoff et al., 2009).
The aim of the project is to identify the cis-regulatory regions acting upstream as information “hubs” to coordinately regulate dose-dependent Blimp1/PRDM1 expression patterns during embryogenesis. Cell marking, chromatin conformation, transgenic analysis and the generation of germ line targeted deletions will be exploited to characterize enhancer elements controlling Blimp1/Prdm1 transcriptional outputs during stem cell maintenance, cell lineage allocation and terminal differentation of specialized cell types.