An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

B and T lymphocyte development is driven by V(D)J recombination, a process by which gene segments at the antigen receptor loci are rearranged to create a vast repertoire of antigen receptor loci. In normal circumstances lymphocytes circumvent the dangers associated with the introduction of multiple double strand breaks (DSBs) through deft co-ordination and tight control over 'where and when' breaks are introduced. Research in the Skok lab, employing a combination of sophisticated imaging and chromosome conformation capture techniques, molecular biology, and genetics, indicates that nuclear dynamics and pairing of homologous and heterologous chromosomal loci controls accessibility to the enzyme that mediates recombination. Such higher-order mechanisms help preserve genomic integrity and regulate gene expression in lymphocytes.