title: An evolutionarily conserved target motif for immunoglobulin class-switch recombination.
abstract: Immunoglobulin H class-switch recombination (CSR) occurs between switch regions and requires transcription and activation-induced cytidine deaminase (AID). Transcription through mammalian switch regions, because of their GC-rich composition, generates stable R-loops, which provide single-stranded DNA substrates for AID. However, we show here that the Xenopus laevis switch region S(mu), which is rich in AT and not prone to form R-loops, can functionally replace a mouse switch region to mediate CSR in vivo. X. laevis S(mu)-mediated CSR occurred mostly in a region of AGCT repeats targeted by the AID-replication protein A complex when transcribed in vitro. We propose that AGCT is a primordial CSR motif that targets AID through a non-R-loop mechanism involving an AID-replication protein A complex.
authors.affiliation: Howard Hughes Medical Institute, The Children's Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Zarrin
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chaudhuri
authors.forename: Nicole
authors.initials: N
authors.lastname: Stokes
authors.forename: Dhruv
authors.initials: D
authors.lastname: Kaushal
authors.forename: Louis
authors.initials: L
authors.lastname: Du Pasquier
authors.forename: Ming
authors.initials: M
authors.lastname: Tian
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics*; D003564:Cytidine Deaminase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003641:Deamination; D019143:Evolution, Molecular; D006825:Hybridomas / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D051716:Replication Protein A; D016415:Sequence Alignment; D013154:Spleen / Q000276:immunology; D014982:Xenopus laevis / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D051716:Replication Protein A; C497168:Rpa1 protein, mouse; D004247:DNA; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase