title: YY1 controls immunoglobulin class switch recombination and nuclear activation-induced deaminase levels.
abstract: Activation-induced deaminase (AID) is an enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM), processes that ensure antibody maturation and expression of different immunoglobulin isotypes. AID function is tightly regulated by tissue- and stage-specific expression, nuclear localization, and protein stability. Transcription factor YY1 is crucial for early B cell development, but its function at late B cell stages is unknown. Here, we show that YY1 conditional knockout in activated splenic B cells interferes with CSR. Knockout of YY1 did not affect B cell proliferation, transcription of the AID and IgM genes, or levels of various switch region germ line transcripts. However, we show that YY1 physically interacts with AID and controls the accumulation of nuclear AID, at least in part, by increasing nuclear AID stability. We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels.
authors.affiliation: Department of Animal Biology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Zaprazna
authors.forename: Michael L
authors.initials: ML
authors.lastname: Atchison
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D013154:Spleen / Q000276:immunology; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase