Chromosome movements that regulate tissue-specific gene expression

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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.