title: Cux/CDP homeoprotein is a component of NF-muNR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator.
abstract: Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (Emu) are the targets of the negative regulator, NF-muNR, found in non-B and early pre-B cells. Expression library screening with NF-muNR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-muNR identity. It is expressed in non-B and early pre-B cells but not mature B cells. It binds to NF-muNR binding sites within Emu with appropriate differential affinities. Antiserum specific for Cux/CDP recognizes a polypeptide of the predicted size in affinity-purified NF-muNR preparations and binds NF-muNR complexed with DNA. Cotransfection with Cux/CDP represses the activity of Emu via the MAR sequences in both B and non-B cells. Cux/CDP antagonizes the effects of the Bright transcription activator at both the DNA binding and functional levels. We propose that Cux/CDP regulates cell-type-restricted, differentiation stage-specific Emu enhancer activity by interfering with the function of nuclear matrix-bound transcription activators.
authors.affiliation: Department of Pathology and Laboratory of Molecular Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9072, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Goldstein
authors.forename: R T
authors.initials: RT
authors.lastname: Zong
authors.forename: D
authors.initials: D
authors.lastname: Lin
authors.forename: E J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: R H
authors.initials: RH
authors.lastname: Scheuermann
authors.forename: P W
authors.initials: PW
authors.lastname: Tucker
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D002461:Cell Line, Transformed; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
chemical_list: C490798:ARID3A protein, human; C097532:Arid3a protein, mouse; C080632:CUX1 protein, human; C000624101:Cux1 protein, mouse; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007148:Immunoglobulin mu-Chains; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors