E-proteins directly regulate expression of activation-induced deaminase in mature B cells.
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.
Sayegh
Camil Elie
CE
Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
Quong
Melanie W
MW
Agata
Yasutoshi
Y
Murre
Cornelis
C
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)
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