In FY13, we accomplished the following: 1) Completed studies of IgH locus conformation in YY1-deficient, YY1-knockdown and CTCF-knockdown pro-B cells using high-resolution 3D-FISH. The results substantiate the predictions of our proposed model for IgH locus architecture in pro-B cells. 2) Dr. Tatiana Gerasimova, our resident expert, collaborated with several extramural investigators to apply short-probe FISH technology to other relevant biological systems. In a collaboration with Dr. Victor Corces (Emory University), we showed that chromatin configuration of ES cell-specific genes was determined by structural proteins predicted from computational studies. In a collaboration with Dr. Amy Kenter (University of Illinois Medical School), we showed that the 3 280 kb of the IgH locus underwent inducible looping in activated B cells preparing for class switch recombination. This loop formation was dependent on YY1 as shown by analysis of YY1-deficient nature B cells (done in collaboration with Dr. Michael Atchison (University of Pennsylvania). 3) Initiated studies with Site 4 mutant mice to visualize IgH alleles in living cells.
| 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 |
