Immunoglobulin genes are known to localize to distinct nuclear compartments during B lineage development and reposition when variable-diversity-joining recombination is occurring. Association with the nuclear lamina silences gene transcription and precludes gene rearrangements. In Cell, Zullo et al. identify GAGA-rich lamina-associated sequences in the immunoglobulin heavy-chain locus (Igh). The entire Igh locus associates with lamin B in fibroblasts. The transcription factor ThPOK, in complex with the histone deacetylase HDAC3 and lamin protein Lap2b, promotes interaction of lamina-associated sequences with the nuclear lamina. Treatment with HDAC inhibitors or knockdown of cKrox or HDAC3 releases Igh; however, reassociation with the nuclear lamina requires passage through mitotic anaphase. How these interactions are developmentally regulated during B cell differentiation remains unknown.

Cell 149, 1474–1487 (2012)