Activation induced cytidine deaminase is an enzyme crucial to somatic hypermutation and gene conversion, processes that are essential for the diversification of Ig V genes. The bovine Ig repertoire appears to be diversified by mechanisms that are significantly different to those that operate in humans and mice. This study set out to test the hypothesis that differences in the organization, coding sequence, expression or genomic location of the bovine AICDA gene enables the encoded enzyme to catalyse the unusual Ig diversification mechanism seen in cattle as well as conventional antigen-driven mutation. Characterization of bovine AICDA excluded the first two possibilities. AICDA expression was detected in lymphoid tissues from neonatal and older cattle, but AICDA cDNA could not be detected in muscle tissue. The pattern of gene expression did not therefore differ from that in other vertebrates. The AICDA cDNA was cloned and expressed successfully in Escherichia coli generating a phenotype consistent with the mutating action of this deaminase. Using a whole genome radiation hybrid panel, bovine AICDA was mapped to a region of bovine chromosome 5 syntenic with the location of human AICDA on chromosome 12. We conclude that the unusual nature of Ig diversification in cattle is unlikely to be attributable to the structure, sequence, activity or genomic location of bovine AICDA.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.vetimm.2009.08.016 | DOI Listing |
Int J Mol Sci
March 2023
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, University of Regensburg, D-93053 Regensburg, Germany.
Cell Reprogram
October 2016
1 Department of Animal Bioscience, College of Agriculture and Life Sciences, Gyeongsang National University, Jinju, Republic of Korea.
Activation-induced cytidine deaminase (AID) is the only enzyme that has been suggested as a putative DNA demethylase in mammals. However, very little is known about AID function as DNA demethylase of bovine differentiated cells toward pluripotent state. To investigate the effect of AID on DNA demethylation, bovine AID complementary DNAs were transfected into bovine differentiated cells, which were mostly methylated in the promoter regions of pluripotency genes.
View Article and Find Full Text PDFCell Reprogram
February 2014
Centre de Recherche en Biologie de la Reproduction, Faculté des Sciences de l'Agriculture et de l'Alimentation, Département des Sciences Animales, Université Laval, Québec, QC, Canada, G1V 0A6 .
Fertilization in bovines causes profound changes in the epigenetic profile that affect both DNA methylation patterns and posttranslational histone modifications. These dynamic changes have a great potential for activating pluripotency genes and unfolding certain chromatin regions to recruit different transcription factors. Surprisingly, while the fundamental function of epigenetic remodeling is well understood, the bases of the process are still unknown.
View Article and Find Full Text PDFMucosal Immunol
September 2013
Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Due to a limited range of immunoglobulin (Ig) genes, cattle and several other domestic animals rely on postrecombinatorial amplification of the primary repertoire. We report that activation-induced cytidine deaminase (AID) is strongly expressed in the fetal bovine ileal Peyer's patch and spleen but not in fetal bone marrow. The numbers of IGHV (immunoglobulin heavy chain variable) mutations correlate with AID expression.
View Article and Find Full Text PDFMol Immunol
September 2011
Laboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045, Japan.
Ig gene hypermutation is initiated by the activation-induced cytidine deaminase (AID), which converts cytosine to uracil and generates a U:G lesion. One of the unsolved mysteries is how AID-triggered U:G lesions result in efficient induction of mutations at non-damaged A/T bases in the V(H) genes of germinal center (GC) B cells. Genetic and biochemical evidence suggests that components of the mismatch repair pathway and the low fidelity DNA polymerase η are required for the induction of A/T mutations.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!