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Chromosome dynamics and the regulation of V(D)J recombination
Author(s) -
Hewitt Susannah L.,
Chaumeil Julie,
Skok Jane A.
Publication year - 2010
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2010.00931.x
Subject(s) - biology , locus (genetics) , recombination , genetics , pax5 , v(d)j recombination , homologous recombination , transcription factor , gene , microbiology and biotechnology
Summary: Perhaps no process has provided more insight into the fine manipulation of locus accessibility than antigen receptor rearrangement. V(D)J recombination is carried out by the lymphoid‐specific recombination‐activating (RAG 1 and 2) proteins and the non‐homologous end joining machinery; yet, it occurs only at specific loci (or portions of loci) during specific developmental stages. This spatiotemporal restriction of recombination is achieved through precise alterations in locus accessibility. In this article, we discuss the work of our laboratory in elucidating how nuclear sublocalization, chromosome conformation, and locus interactions contribute to regulating this complex process. We also discuss what is known about how key factors in B‐cell development (such as the ubiquitously expressed helix loop helix protein E2A, the B‐cell specific transcription factors EBF1 and Pax5, and the interleukin‐7 cytokine signaling pathway) exert their effects through changes in nuclear dynamics.