During FY14 we accomplished the following: 1. Completed studies on the step-wise establishment of tissue-specific chromosome conformation of the IgH locus. Specifically we found the CTCF-dependent locus compacting interactions did not require Pax5 or E. However E-dependent long-range interactions required both YY1 and Pax5. All loop formation occurred only in B lineage cells. These studies were carried out in collaboration Dr. Ann Feeney (The Scripps Research Institute, San Diego). 2. We developed the use of 3-4kb FISH probes for high resolution FISH studies of chromosome conformation. We used these probes to study inter-chromosomal interaction between IgH and c-Myc loci on chromosomes 12 and 15, respectively. 3. We assayed IgH locus conformation in primary bone marrow pro-B cells from old mice. Preliminary experiments indicate severely attenuated locus compaction in old pro-B cells. Such de-compaction may lead to reduced efficiency of VDJ recombination with age, and result in a smaller repertoire of B cells available for effective immunity.
| Lovely, Geoffrey A; Sen, Ranjan (2016) Evolving adaptive immunity. Genes Dev 30:873-5 |
| Sen, Ranjan (2016) A Pioneer's Tail. Immunity 44:516-8 |
| 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 |
