Regulation of matrix attachment region-dependent, lymphocyte-restricted transcription through differential localization within promyelocytic leukemia nuclear bodies.
Bright (B cell regulator of IgH transcription) transactivates the immunoglobulin heavy chain (IgH) intronic enhancer, Emicro, by binding to matrix attachment regions (MARs), sites necessary for DNA attachment to the nuclear matrix. Here we report that Bright interacts with the ubiquitous autoantigen Sp100, a component of promyelocytic leukemia nuclear bodies (PML NBs), and with LYSp100B/Sp140, the lymphoid-restricted homolog of Sp100. Both in intact cells and in nuclear matrix preparations, the majority of Bright and Sp100 colocalize within PML NBs. In contrast, Bright colocalizes with only a small fraction of LYSp100B while inducing a redistribution of the majority of 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 significantly higher levels than Sp100 to inhibit MAR binding. However, it strongly stimulates Bright transactivation through E mu. We suggest that Sp100 and LYSp100B interactions with Bright have different consequences for IgH transcription, potentially through differential association of E mu MARs with nuclear matrix- associated PML NBs and LANDs.
Department of Molecular Genetics and The Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.
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D034961:Antigens, Nuclear; D001324:Autoantigens / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute; D008969:Molecular Sequence Data; D015530:Nuclear Matrix; D009687:Nuclear Proteins / Q000378:metabolism*; D009857:Oncogenes; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
C490798:ARID3A protein, human; D034961:Antigens, Nuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C066642:SP100 protein, human