Epigenetic Histone Modifications Do Not Control Igκ Locus Contraction and Intranuclear Localization in Cells with Dual B Cell-Macrophage Potential1

Somatic rearrangement of the Ig genes during B cell development is believed to be controlled, at least in part, by accessibility of the loci to the recombinational machinery. Accessibility is poorly understood, but appears to be controlled by a combination of histone posttranslational modifications, large scale Ig locus contractions, and changes in intranuclear localization of the loci. These changes are regulated by developmental stage-specific as well as tissue-specific mechanisms. We previously isolated a murine B cell lymphoma line, Myc5, that can oscillate between the B cell and macrophage lineages depending upon growth conditions. This line provides an opportunity to study tissue-specific regulation of epigenetic mechanisms operating on the Ig loci. We found that when Myc5 cells are induced to differentiate from B cells into macrophages, expression of macrophage-specific transcripts was induced (M-CSFR , F4/80, and CD14), whereas B cell-specific transcripts decreased dramatically (mb-1, E47, IRF4, Pax5, and Igκ). Loss of Igκ transcription was associated with reduced Ig κ locus contraction, as well as increased association with heterochromatin protein-1 and association of the Ig κ locus with the nuclear periphery. Surprisingly, however, we found that histone modifications at the Ig κ locus remained largely unchanged whether the cells were grown in vivo as B cells, or in vitro as macrophages. These results mechanistically uncouple histone modifications at the Igκ locus from changes in locus contraction and intranuclear localization.