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

Open Access
Publisher Website
Google Scholar
Abstract
We have sequenced the entire human Sμ and S-γ4 immunoglobulin heavy chain class switch regions, and have also completed the sequence of human Sε. Sμ is composed predominantly of GAGCT and GGGCT pentameric repeats, with these units also being found in Sε at a much tower density. Sμ-Sγ4 matches are infrequent, but Sγ4 contains a cluster of repeated sequences similar to units in mouse γ switch sites and unrelated to the Sμ repeats, suggesting that Sμ-Sγ homology is not important in μ-γ switching. We examined our ε and γ4 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 Sε regions that overlaps and extends 5′ to the start sites for human and mouse ε sterile transcripts. Similarly, an ECS upstream from Sγ4 is homologous to a mouse sequence that overlaps and extends 5′ to the start sites for mouse γ2b sterile transcripts. The ε and γ4 conserved segments contain potential interferon Stimulable Response Elements (ISRE's) that are identical between human εand γ4.