Sequences of human immunoglobulin switch regions: implications for recombination and transcription.
We have sequenced the entire human S mu and S gamma 4 immunoglobulin heavy chain class switch regions, and have also completed the sequence of human S epsilon. S mu is composed predominantly of GAGCT and GGGCT pentameric repeats, with these units also being found in S epsilon at a much lower density. S mu-S gamma 4 matches are infrequent, but S gamma 4 contains a cluster of repeated sequences similar to units in mouse gamma switch sites and unrelated to the S mu repeats, suggesting that S mu-S gamma homology is not important in mu-gamma switching. We examined our epsilon and gamma 4 sequences for features that could regulate production of 'sterile' transcripts preceding switch recombination. There is an Evolutionarily Conserved Sequence (ECS) upstream from the human and mouse S epsilon regions that overlaps and extends 5' to the start sites for human and mouse epsilon sterile transcripts. Similarly, an ECS upstream from S gamma 4 is homologous to a mouse sequence that overlaps and extends 5' to the start sites for mouse gamma 2b sterile transcripts. The epsilon and gamma 4 conserved segments contain potential Interferon Stimulable Response Elements (ISRE's) that are identical between human epsilon and gamma 4.
Mills
F C
FC
Genetics and Biochemistry Branch, NIDDK, NIH, Bethesda, MD 20892.
Brooker
J S
JS
Camerini-Otero
R D
RD
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains