THE IMMUNOGLOBULIN HEAVY-CHAIN MATRIX-ASSOCIATING REGIONS ARE BOUND BY BRIGHT - A B-CELL-SPECIFIC TRANSACTIVATOR THAT DESCRIBES A NEW DNA-BINDING PROTEIN FAMILY

B lymphocyte-restricted transcription of immunoglobulin heavy-chain (I gH) genes is specified by elements within the variable region (V-H) pr omoter and the intronic enhancer (E mu). The gene encoding a protein t hat binds a V-H promoter proximal site necessary for induced mu-heavy- chain transcription has been cloned. This B-cell specific protein, ter med Bright (B cell regulator of IgH transcription), is found in both s oluble and matrix insoluble nuclear fractions. Bright binds the minor groove of a restricted ATC sequence that is sufficient for nuclear mat rix association. This sequence motif is present in previously describe d matrix-associating regions (MARs) proximal to the promoter and flank ing E mu. Bright can activate E mu-driven transcription by binding the se sites, but only when they occur in their natural context and in cel l lines permissive for E mu activity. To bind DNA, Bright requires a n ovel tetramerization domain and a previously undescribed domain that s hares identity with several proteins, including SWI1, a component of t he SWI/SNF complex.