Distinct regulatory mechanisms for interferon-alpha/beta (IFN-alpha/beta)- and IFN-gamma-mediated induction of Ly-6E gene in B cells.
The murine Ly6-E gene is transcriptionally induced by interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma in a variety of distinct cell types. The mechanism of IFN inducibility in B-cell lines was investigated by deletion analysis of the promoter and by identifying DNA binding proteins in mobility shift assays. A region located in the distal part of the promoter at -2.3 kb contributed to inducibility by both types of IFNs. This region contains a novel element in addition to the previously well-characterized IFN-stimulated response element (ISRE). The probes containing ISRE detected IFN-inducible complexes in mobility shift assays and the signal transducer and activator of transcripition-1 was found to be in these complexes from cells treated with either type of IFN. An additional element present in the proximal part of the promoter at position -109 is also required for IFN-alpha/beta-mediated induction. These data suggested a cooperative interaction between these physically disparate regulatory regions. A crucial role for HMGI(Y) protein in this cooperative multiprotein complex is supported by the evidence that inhibition of HMGI(Y) expression via antisense RNA results in the loss of IFN-alpha/beta-mediated induction of the Ly6-E gene. These results show the complexity involved in achieving cell-type specificity in IFN-mediated gene regulation.
Khodadoust
M M
MM
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
Khan
K D
KD
Park
E H
EH
Bothwell
A L
AL
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis* / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects*; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000502:physiology*; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D016393:Lymphoma, B-Cell / Q000473:pathology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D006609:High Mobility Group Proteins; D016898:Interferon-alpha; C074650:Ly6a protein, mouse; D046911:Macromolecular Substances; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D014157:Transcription Factors; D025741:HMGA1a Protein; D016899:Interferon-beta; D007371:Interferon-gamma