title: Zfp318 regulates IgD expression by abrogating transcription termination within the Ighm/Ighd locus.
abstract: The protein Zfp318 is expressed during the transition of naive B cells from an immature to mature state. To evaluate its role in mature B cell functions, a conditional gene deficiency in Zfp318 was created and deleted in bone marrow lineages via Vav-Cre. B cell development was minimally altered in the absence of the protein, although transitional 2 (T2) B cell populations were depressed in the absence of Zfp318. Intriguingly, the analysis of IgM and IgD expression by maturing and mature naive B cells demonstrated an elevated level of IgM gene products and a virtual loss of IgD products. Transcriptome analysis of Zfp318-deficient B cells revealed that only two gene products showed altered expression in the absence of Zfp318 (Ighd and Sva), demonstrating a remarkable specificity of Zfp318 action. In the absence of Zfp318, Ighm/Ighd transcripts, which would normally encode IgM and IgD from heterogeneous nuclear RNA transcripts via alternative splicing, lack intron and exon sequences from the IgD (Ighd)-encoding region. This finding indicates that Zfp318, in a novel manner, functions by repressing recognition of the transcriptional termination site at the 3' end of the terminal IgM-encoding exon, allowing for synthesis of the complete Ighm/Ighd heterogeneous nuclear RNA.
authors: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
authors: Peter D
authors: PD
authors: Pioli
authors: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
authors: Irina
authors: I
authors: Debnath
authors: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112.
authors: Janis J
authors: JJ
authors: Weis
authors: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112 john.weis@path.utah.edu.
authors: John H
authors: JH
authors: Weis
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005091:Exons / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D056426:Genetic Loci / Q000276:immunology*; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology*; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D061806:Transcription Termination, Genetic / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; D007072:Immunoglobulin D; D007075:Immunoglobulin M