title: Characterization of a new ARID family transcription factor (Brightlike/ARID3C) that co-activates Bright/ARID3A-mediated immunoglobulin gene transcription.
abstract: Two members, Bright/ARID3A and Bdp/ARID3B, of the ARID (AT-Rich Interaction Domain) transcription family are distinguished by their ability to specifically bind to DNA and to self-associate via a second domain, REKLES. Bright and Bdp positively regulate immunoglobulin heavy chain gene (IgH) transcription by binding to AT-rich motifs within Matrix Associating Regions (MARs) residing within a subset of V(H) promoters and the Eμ intronic enhancer. In addition, REKLES provides Bright nuclear export function, and a small pool of Bright is directed to plasma membrane sub-domains/lipid rafts where it associates with and modulates signaling of the B cell antigen receptor (BCR). Here, we characterize a third, highly conserved, physically condensed ARID3 locus, Brightlike/ARID3C. Brightlike encodes two alternatively spliced, SUMO-I-modified isoforms that include or exclude (Δ6) the REKLES-encoding exon 6. Brightlike transcripts and proteins are expressed preferentially within B lineage lymphocytes and coordinate with highest Bright expression in activated follicular B cells. Brightlike, but not BrightlikeΔ6, undergoes nuclear-cytoplasmic shuttling with a fraction localizing within lipid rafts following BCR stimulation. Brightlike, but not BrightlikeΔ6, associates with Bright in solution, at common DNA binding sites in vitro, and is enriched at Bright binding sites in chromatin. Although possessing little transactivation capacity of its own, Brightlike significantly co-activates Bright-dependent IgH transcription with maximal activity mediated by the unsumoylated form. In sum, this report introduces Brightlike as an additional functional member of the family of ARID proteins, which should be considered in regulatory circuits, previously ascribed to be mediated by Bright.
authors.affiliation: Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Josephine A
authors.initials: JA
authors.lastname: Tidwell
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidt
authors.forename: Phillip
authors.initials: P
authors.lastname: Heaton
authors.forename: Van
authors.initials: V
authors.lastname: Wilson
authors.forename: Philip W
authors.initials: PW
authors.lastname: Tucker
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002469:Cell Separation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics* / Q000276:immunology; D006801:Humans; D047468:Immunoprecipitation; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics* / Q000276:immunology
chemical_list: C490798:ARID3A protein, human; C568691:ARID3C protein, human; C568692:Arid3c protein, mouse; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D014157:Transcription Factors