The balance between Pax5 and Id2 activities is the key to AID gene expression.
Pax5 activity is enhanced in activated B cells and is essential for class switch recombination (CSR). We show that inhibitor of differentiation (Id)2 suppresses CSR by repressing the gene expression of activation-induced cytidine deaminase (AID), which has been shown to be indispensable for CSR. Furthermore, a putative regulatory region of AID contains E2A- and Pax5-binding sites, and the latter site is indispensable for AID gene expression. Moreover, the DNA-binding activity of Pax5 is decreased in Id2-overexpressing B cells and enhanced in Id2(-/-) B cells. The kinetics of Pax5, but not E2A, occupancy to AID locus is the same as AID expression in primary B cells. Finally, enforced expression of Pax5 induces AID transcription in pro-B cell lines. Our results provide evidence that the balance between Pax5 and Id2 activities has a key role in AID gene expression.
Gonda
Hiroyuki
H
Center for Molecular Biology and Genetics, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Sugai
Manabu
M
Nambu
Yukiko
Y
Katakai
Tomoya
T
Agata
Yasutoshi
Y
Mori
Kazuhiro J
KJ
Yokota
Yoshifumi
Y
Shimizu
Akira
A
D000818:Animals; D001483:Base Sequence; D003564:Cytidine Deaminase / Q000235:genetics*; D004247:DNA; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051757:PAX5 Transcription Factor; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D017931:DNA Primers; D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase