Regulation of matrix attachment region-dependent, lymphocyte-restricted transcription through differential localization within promyelocytic leukemianuclear bodies

Bright (B cell regulator of IgH transcription) transactivates the immunoglo bulin heavy chain (IgH) intronic enhancer, E mu, by binding to matrix attac hment regions (MARs), sites necessary for DNA attachment to the nuclear mat rix. Here we report that Bright interacts with the ubiquitous autoantigen S p100, a component of promyelocytic leukemia nuclear bodies (PML NBs), and w ith LYSp100B/ Sp140, the lymphoid-restricted homolog of Sp100. Both in inta ct cells and in nuclear matrix preparations, the majority of Bright and Sp1 00 colocalize within PML NBs, In contrast, Bright colocalizes with only a s mall fraction of LYSp100B while inducing a redistribution of the majority o f LYSp100B from its associated nuclear domains (LANDs) into nucleoplasm and cytoplasm, Sp100 represses the MAR-binding and transactivation activity of Bright. LYSp100B interacts more weakly with Bright but requires significan tly higher levels than Sp100 to inhibit MAR binding, However, it strongly s timulates Bright transactivation through E mu. We suggest that Sp100 and LY Sp100B interactions with Bright have different consequences for IgH transcr iption, potentially through differential association of E mu MARs with nucl ear matrix-associated PML NBs and LANDs.