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 of human and mouse epsilon sterile transcripts. Similarly, and 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.