title: APRIL stimulates NF-κB-mediated HoxC4 induction for AID expression in mouse B cells.
abstract: Activation-induced cytidine deaminase (AID) plays a key role in B cell immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM). We have previously reported that the highly conserved homeodomain HoxC4 transcription factor binds to the Aicda (AID gene) promoter to induce AID expression. Here, we investigated the regulation of HoxC4 transcription by a proliferation-inducing ligand (APRIL) and B cell-activating factor belonging to the TNF family (BAFF) in mouse B cells. APRIL substantially increased both HoxC4 and AID expression, whereas BAFF induced the expression of AID but not HoxC4. To elucidate the underlying mechanisms, we constructed a HoxC4 gene promoter reporter vector and analyzed the promoter induction after APRIL stimulation. APRIL enhanced the HoxC4 promoter activity by 2.3-fold, and this increase disappeared when the second putative NF-κB-binding promoter element (NBE2) was mutated. Based on ChIP assays, we found that NF-κB bound to the HoxC4 promoter NBE2 region. Furthermore, the overexpression of NF-κB augmented the APRIL-induced HoxC4 promoter activity, while the expression of dominant negative-IκBα suppressed it. Taken together, our findings suggest that NF-κB mediates APRIL-induced HoxC4 transcription.
authors.affiliation: Department of Microbiology, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea. srpark@konyang.ac.kr
authors.forename: Seok-Rae
authors.initials: SR
authors.lastname: Park
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Lee
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Goo-Young
authors.initials: GY
authors.lastname: Seo
authors.forename: Yung-Choon
authors.initials: YC
authors.lastname: Yoo
authors.forename: Junglim
authors.initials: J
authors.lastname: Lee
authors.forename: Paolo
authors.initials: P
authors.lastname: Casali
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D018398:Homeodomain Proteins; C490904:Hoxc4 protein, mouse; D016328:NF-kappa B; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase