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.
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Dempsey, L. Nuclear silencing. Nat Immunol 13, 946 (2012). https://doi.org/10.1038/ni.2444
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DOI: https://doi.org/10.1038/ni.2444