Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Tatiana Gerasimova
Accepted Abstracts: J Clin Cell Immunol
Immunoglobulin heavy chain (IgH) genes are assembled by rearrangement of variable (V H ), diversity (D H ) and joining (J H ) gene segments spread over more than 2.5 Mb of the genome. The order of recombination is precisely determined, with DH to JH recombination occurring first, followed by VH recombination to newly-created DJH junctions. One key mechanism involves folding of the IgH locus into conformations that minimize hazardous translocation events during V(D)J recombination. In a previous study we proposed a two-step model for generating IgH locus conformation. The first step, which is Eμ-independent, permits pro-B-specific CTCF binding to the Ig H locus and generates multiple 250-400 kb sub-domains. The second step involves Eμ-dependent interactions with distant sites in the V H region that juxtapose sub-domains in the V H part of the locus to the 3? end of the IgH locus, thereby leading to locus compaction. Here we verify that Eμ-dependent interactions with the V H regions are involved in locus compaction and demonstrate that integrity of Eμ-dependent loops requires YY1 protein. We also provide evidence that YY1-dependent locus compaction is mediated by the condensin components Smc 2 and 4. In contrast, sub-domains in the VH are CTCF dependent but YY1- independent. Furthermore, these CTCF-dependent sub-domains are B lineage-specific and Pax5-independent. These observations strongly substantiate the hypothesis that IgH locus compaction occurs by two independently-regulated steps that first fold the entire locus into sub-domains followed by juxtaposition of sub-domains to accomplish full contraction. Using novel multi-probe FISH technique we also demonstrated a great variability and diversity of chromatin conformation even inside one genotype using IgH mouse locus. We suggest that these folding principles may apply more generally in folding megabase-sized chunks of the genome.
Tatiana Gerasimova received her education, PhD and Doctorate degree in Moscow, Russia. She worked in the Biology Department of Johns Hopkins University, USA, where she made significant contributions in molecular genetics of Drosophila melanogaster, in characterization of Insulators elements. During 15 years she was an Associate Editor of journal ?Genetica? ((The International Journal of Genetics, Springer, Netherlands). She has published more than 100 papers in peer-reviewed journals, including Nature, Cell, Molecular Cell, Genes and Development, etc. Since 2007, she is a Staff Scientist of the National Institute of Aging, Laboratory of Molecular Biology and Immunology. During these years she dedicated herself to investigate chromatin structure and nuclear architecture of the murine immunoglobulin heavy chain (IgH) gene using 3D-multicolor FISH technique.