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Nucleic Acids Research, 1990, Vol. 18, No. 24 7305-7316
© 1990


Articles

Sequences of human immunoglobulin switch regions: implications for recombination and transcription

Frederick C. Mills, Jeffrey S. Brooker and R.Daniel Camerini-Otero*

Genetics and Biochemistry Branch, NIDDK Building 10, Room 9D15, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA

*To whom correspondence should be addressed

Received September 19, 1990. Revised November 12, 1990. Accepted November 12, 1990.

We have sequenced the entire human Sµ and S-{gamma}4 immunoglobulin heavy chain class switch regions, and have also completed the sequence of human S{varepsilon}. Sµ is composed predominantly of GAGCT and GGGCT pentameric repeats, with these units also being found in S{varepsilon} at a much tower density. Sµ-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 Sµ repeats, suggesting that Sµ-S{gamma} homology is not important in µ-{gamma} switching. We examined our {varepsilon} 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{varepsilon} regions that overlaps and extends 5' to the start sites for human and mouse {varepsilon} 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 {varepsilon} and {gamma}4 conserved segments contain potential interferon Stimulable Response Elements (ISRE's) that are identical between human {varepsilon}and {gamma}4.


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