A long standing goal of immunogenetics has been to understand the genetic basis of antibody diversity and responsiveness, the mechanisms through which the apparently limitless variety of antibody sequences are created.
Our aim i s to complete the determination of the structure, and the complete sequence, of the immunoglobulin heavy chain (Igh) locus in two strains of mice that have markedly different Igh gene complexes; we will complete the assembly of sequence-ready Bacterial Artificial Chromosome (BAG) contigs from C57BL/6 and 129/Sv; we will identify every variable region (Vh) gene with their 5' and 3' regulatory and RSS elements and compare these germline specificity repertoires. Comparison of the two mouse haplotypes will also reveal conserved noncoding sequence elements; these will likely include control elements used in the regulation of this complex locus, and we will investigate their possible roles in regulating the activation, expression, and replication of Igh. ? ? ?

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Cellular and Molecular Immunology - A Study Section (CMIA)
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Macchiarini, Francesca
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Torrey Pines Institute for Molecular Studies
Port St. Lucie
United States
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Degner, Stephanie C; Verma-Gaur, Jiyoti; Wong, Timothy P et al. (2011) CCCTC-binding factor (CTCF) and cohesin influence the genomic architecture of the Igh locus and antisense transcription in pro-B cells. Proc Natl Acad Sci U S A 108:9566-71
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Retter, Ida; Chevillard, Christophe; Scharfe, Maren et al. (2007) Sequence and characterization of the Ig heavy chain constant and partial variable region of the mouse strain 129S1. J Immunol 179:2419-27
Pawlitzky, Inka; Angeles, Christina V; Siegel, Andrea M et al. (2006) Identification of a candidate regulatory element within the 5' flanking region of the mouse Igh locus defined by pro-B cell-specific hypersensitivity associated with binding of PU.1, Pax5, and E2A. J Immunol 176:6839-51
Norio, Paolo; Kosiyatrakul, Settapong; Yang, Qiaoxin et al. (2005) Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development. Mol Cell 20:575-87
Yang, Qiaoxin; Riblet, Roy; Schildkraut, Carl L (2005) Sites that direct nuclear compartmentalization are near the 5' end of the mouse immunoglobulin heavy-chain locus. Mol Cell Biol 25:6021-30
Jones Tiffany, Linda; Riblet, Roy; Stein, Kathryn E (2003) The Sr1 gene that controls diversity of the anti-inulin antibody response maps to mouse chromosome 14. Immunogenetics 55:80-6
Chevillard, Christophe; Ozaki, Jennifer; Herring, Christopher D et al. (2002) A three-megabase yeast artificial chromosome contig spanning the C57BL mouse Igh locus. J Immunol 168:5659-66
Zhou, Jie; Ermakova, Olga V; Riblet, Roy et al. (2002) Replication and subnuclear location dynamics of the immunoglobulin heavy-chain locus in B-lineage cells. Mol Cell Biol 22:4876-89
Zhou, Jie; Ashouian, Nasrin; Delepine, Marc et al. (2002) The origin of a developmentally regulated Igh replicon is located near the border of regulatory domains for Igh replication and expression. Proc Natl Acad Sci U S A 99:13693-8

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