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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000373-06
Application #
8736546
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$609,058
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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