Cux/CDP homeoprotein is a component of NF-mu NR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator

Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (E mu) are the targets of the negative regulator, N F-mu NR, found in non-B and early pre-B cells. Expression library screening with NF-mu NR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-mu NR identity. It is expressed in non-B and early pre-B c ells but not mature B cells. It binds to NF-mu NR binding sites within E mu with appropriate differential affinities. Antiserum specific for Cux/CDP r ecognizes a polypeptide of the predicted size in affinity-purified NF-mu NR preparations and binds NF-mu NR complexed with DNA. Cotransfection with Cu x/CDP represses the activity of E mu via the MAR sequences in both B and no n-B cells. Cux/CDP antagonizes the effects of the Bright transcription acti vator at both the DNA binding and functional levels. We propose that Cux/CD P regulates cell-type-restricted, differentiation stage-specific E mu enhan cer activity by interfering with the function of nuclear matrix-bound trans cription activators.