Chromosome dynamics and the regulation of V(D)J recombination

SL Hewitt, J Chaumeil, JA Skok - Immunological reviews, 2010 - Wiley Online Library
SL Hewitt, J Chaumeil, JA Skok
Immunological reviews, 2010Wiley Online Library
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 …
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.
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