title: Cutting edge: a cis-acting DNA element targets AID-mediated sequence diversification to the chicken Ig light chain gene locus.
abstract: 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.
authors.affiliation: 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.
authors.forename: Nagarama
authors.initials: N
authors.lastname: Kothapalli
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Norton
authors.forename: Sebastian D
authors.initials: SD
authors.lastname: Fugmann
mesh_terms: 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)
chemical_list: D005819:Genetic Markers; D007147:Immunoglobulin Light Chains; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase