title: E-proteins directly regulate expression of activation-induced deaminase in mature B cells.
abstract: Activated mature B cells in which the DNA-binding activity of E-proteins has been disrupted fail to undergo class switch recombination. Here we show that activated B cells overexpressing the antagonist helix-loop-helix protein Id3 do not induce expression of the murine Aicda gene encoding activation-induced deaminase (AID). A highly conserved intronic regulatory element in Aicda binds E-proteins both in vitro and in vivo. The transcriptional activity of this element is regulated by E-proteins. We show that the enforced expression of AID in cells overexpressing Id3 partially restores class switch recombination. Taken together, our observations link helix-loop-helix activity and Aicda gene expression in a common pathway, in which E-protein activity is required for the efficient induction of Aicda transcription.
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Camil Elie
authors.initials: CE
authors.lastname: Sayegh
authors.forename: Melanie W
authors.initials: MW
authors.lastname: Quong
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D004742:Enhancer Elements, Genetic / Q000276:immunology; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology*; D018257:Helix-Loop-Helix Motifs / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004268:DNA-Binding Proteins; D007132:Immunoglobulin Isotypes; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase