About the Project
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.
Mould, A., Morgan, M.A., Nelson, A., Bikoff, E.K., and Robertson, E.J. (2015). Blimp1/Prdm1 functions in opposition to Irf1 to maintain neonatal tolerance during postnatal intestinal maturation. PLoS Genet. 2015 Jul 9;11(7):e1005375
Mould, A., Morgan M.A.J., Li, L., Bikoff, E. K., and Robertson, E. J. (2012). Blimp1/Prdm1 governs terminal differentiation of endovascular trophoblast giant cells and defines multipotent progenitors in the developing placenta. Genes & Dev 26, 2063-74.
Harper, J., Mould, A., Andrews, R. Bikoff, E., and Robertson E.J. (2011) The transcriptional repressor Blimp1/Prdm1 regulates post-natal reprogramming of intestinal enterocytes. Proc Natl Acad Sci U S A. 108, 10585-90
Bikoff, E.K, Morgan, M.A., and Robertson, E.J. (2009). An expanding job description for Blimp1/PRDM1. Current Opinion Genet. Dev. 19, 379-85.
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