1: Mol Immunol. 2005 Jul 5; [Epub ahead of print] 

Identification of a ubiquitously active promoter of the murine
activation-induced cytidine deaminase (AICDA) gene.

Yadav A, Olaru A, Saltis M, Setren A, Cerny J, Livak F.

Department of Microbiology and Immunology, School of Medicine, University of
Maryland at Baltimore, 655 West Baltimore St, BRB 13-017, Baltimore, MD 21201,
USA.

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.

PMID: 16005067 [PubMed - as supplied by publisher]


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