Differential Regulation of Immunoglobulin Gene Transcription via Nuclear Matrix-associated Regions

We have identified a nuclear-matrix-associated, Bcell-restricted regulator of IgH transcription (Bright)(Herrscher et al. 1995). Bright binds and trans-activatesvia specific A/T-rich sequences (MARs) within and necessary for nuclear matrix attachment of the IgH intronicenhancer (Eµ). We have found that a previously identified protein, Cux/CDP, which resides within matrices ofnon-B and early lineage-B (pre-B) cells, represses Eµ viathe same binding sites bound by Bright in more differentiated B cells (Wang et al. 1999). Cux can effectively antagonize Bright binding and trans-activation and appearsto comprise (at least in part) a previously identified protein/DNA complex, NF-µNR (nuclear factor implicatedin µ IgH negative regulation) (Scheuermann and Chen1989). We hypothesize that the reciprocal action of thesefactors contributes to the cell-type-restricted on/off stateof Eµ and to the increase in Eµ activity during B-cell lineage development/differentiation. We suggest that anovel and potentially rate-limiting consequence is toswitch the balance of IgH nuclear matrix attachment.Here, we discuss the structure, function, and expressionof Bright, Cux/CDP, and molecules that interact withthem in the context of this model...