title: Positive regulatory domain I-binding factor 1 mediates repression of the MHC class II transactivator (CIITA) type IV promoter.
abstract: MHC class II transactivator (CIITA), a co-activator that controls MHC class II (MHC II) transcription, functions as the master regulator of MHC II expression. Persistent activity of the CIITA type III promoter (pIII), one of the four potential promoters of this gene, is responsible for constitutive expression of MHC II by B lymphocytes. In addition, IFN-gamma induces expression of CIITA in these cells through the type IV promoter (pIV). Positive regulatory domain 1-binding factor 1 (PRDI-BF1), called B lymphocyte-induced maturation protein 1 (Blimp-1) in mice, represses the expression of CIITA pIII in plasma and multiple myeloma cells. To investigate regulation of CIITA pIV expression by PRDI-BF1 in the B lymphocyte lineage, protein/DNA-binding studies, and functional promoter analyses were performed. PRDI-BF1 bound to the IFN regulatory factor-element (IRF-E) site in CIITA pIV. Ectopic expression of either PRDI-BF1 or Blimp-1 repressed this promoter in B lymphocytes. In vitro binding and functional analyses of CIITA pIV demonstrated that the IRF-E is the target of this repression. In vivo genomic footprint analysis demonstrated protein binding at the IRF-E site of CIITA pIV in U266 myeloma cells, which express PRDI-BF1. PRDI-BF1beta, a truncated form of PRDI-BF1 that is co-expressed in myeloma cells, also bound to the IRF-E site and repressed CIITA pIV. These findings demonstrate for the first time that, in addition to silencing expression of CIITA pIII in B lymphocytes, PRDI-BF1 is capable of binding and suppressing CIITA pIV.
authors.affiliation: Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St., Macon, GA 31207, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Gilbert
authors.forename: John A
authors.initials: JA
authors.lastname: Hudson
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Bolick
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Wright
authors.forename: Janet F
authors.initials: JF
authors.lastname: Piskurich
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1