Identification of a ubiquitously active promoter of the murine activation-induced cytidine deaminase (AICDA) gene.
Somatic hypermutation and class switch recombination of immunoglobulin genes are dependent on the presence of the activation-induced cytidine deaminase (AICDA) enzyme. AICDA expression is restricted to activated B-lymphocytes in the germinal centers. It has been suggested that inappropriate expression of AICDA may lead to genome instability and aberrant affinity maturation of putative autoreactive antibodies. To better understand the molecular control of its tightly regulated expression we have identified the transcription initiation site and an upstream, conserved promoter region of the murine AICDA gene. The promoter lacks a consensus TATA box but contains an initiator (Inr) element and is active in several murine and human cell lines irrespective of endogenous AICDA expression. Mutagenesis analysis identified a functionally important Sp-binding site which binds both Sp1 and Sp3 in vitro in all cell types. Contrary to a recent report, no evidence was found for direct Pax5-binding at this DNA site. We discuss the role of ubiquitous and lymphoid-specific factors in the control of AICDA gene transcription.
Yadav
Anjana
A
Department of Microbiology and Immunology, School of Medicine, University of Maryland at Baltimore, 655 West Baltimore St, BRB 13-017, Baltimore, MD 21201, USA.
Olaru
Alexandru
A
Saltis
Mark
M
Setren
Adam
A
Cerny
Jan
J
Livák
Ferenc
F
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D017124:Conserved Sequence; D003564:Cytidine Deaminase / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; D024363:Transcription Initiation Site; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase