Cutting edge: a cis-acting DNA element targets AID-mediated sequence diversification to the chicken Ig light chain gene locus.
Somatic hypermutation and gene conversion are two closely related processes that increase the diversity of the primary Ig repertoire. Both processes are initiated by the activation-induced cytidine deaminase that converts cytosine residues to uracils in a transcription-dependent manner; these lesions are subsequently fixed in the genome by direct replication and error-prone DNA repair. Two alternative mechanisms were proposed to explain why this mutagenic activity is targeted almost exclusively to Ig loci: 1) specific cis-acting DNA sequences; or 2) very high levels of Ig gene transcription. In this study we now identify a novel 3' regulatory region in the chicken Ig light chain gene containing not only a classical transcriptional enhancer but also cis-acting DNA elements essential for targeting activation-induced cytidine deaminase-mediated sequence diversification to this locus.
Kothapalli
Nagarama
N
Molecular Immunology Unit, Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Norton
Darrell D
DD
Fugmann
Sebastian D
SD
D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D002460:Cell Line; D002645:Chickens; D003564:Cytidine Deaminase / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000276:immunology; D005785:Gene Conversion / Q000235:genetics / Q000276:immunology; D018390:Gene Targeting; D005819:Genetic Markers / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics* / Q000378:metabolism*; D016254:Mutagenesis, Insertional; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology*; D017384:Sequence Deletion / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D005819:Genetic Markers; D007147:Immunoglobulin Light Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase