Progress during FY18: 1) Continued live-cell imaging of RAG proteins in the nuclei of pro-B cells. These studies identified possible interactions of the non-core domain of RAG1 with nuclear components. In collaboration with David Schatzs laboratory (Yale University), we are testing the interaction of this domain with various forms of histone modifications. 2) Completed studies in DP thymocytes examining partial activation of IgH gene rearrangements in these cells. Our observations indicate that inappropriate enhancer activation underlies some of the phenotypes of IgH alleles in DP cells. Particularly striking were the absence of Ets-1 and E47 binding to E in DP cells, despite comparable expression of these factors in DP and pro-B cells. E was also marked with higher levels of H3K4me1 rather than H3K27ac in DP cells compared to pro-B cells, indicating that the enhancer was primed but not fully active. These observations lay the foundation for future studies aimed at understanding the transition of tissue-specific enhancers from a primed to an active state.
| Sen, Ranjan (2016) A Pioneer's Tail. Immunity 44:516-8 |
| Lovely, Geoffrey A; Sen, Ranjan (2016) Evolving adaptive immunity. Genes Dev 30:873-5 |
| Feldman, Scott; Achour, Ikbel; Wuerffel, Robert et al. (2015) Constraints contributed by chromatin looping limit recombination targeting during Ig class switch recombination. J Immunol 194:2380-9 |
| Gerasimova, Tatiana; Guo, Changying; Ghosh, Amalendu et al. (2015) A structural hierarchy mediated by multiple nuclear factors establishes IgH locus conformation. Genes Dev 29:1683-95 |
| Phillips-Cremins, Jennifer E; Sauria, Michael E G; Sanyal, Amartya et al. (2013) Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153:1281-95 |
| Subrahmanyam, Ramesh; Sen, Ranjan (2012) Epigenetic features that regulate IgH locus recombination and expression. Curr Top Microbiol Immunol 356:39-63 |
| Guo, Changying; Gerasimova, Tatiana; Hao, Haiping et al. (2011) Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus. Cell 147:332-43 |
