| First Author | Zhou X | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 12 | Pages | 7544-52 |
| PubMed ID | 21076060 | Mgi Jnum | J:167472 |
| Mgi Id | MGI:4868326 | Doi | 10.4049/jimmunol.1002665 |
| Citation | Zhou X, et al. (2010) The Igkappa gene enhancers, E3' and Ed, are essential for triggering transcription. J Immunol 185(12):7544-52 |
| abstractText | The mouse Igkappa gene locus has three known transcriptional enhancers: an intronic enhancer (Ei), a 3' enhancer (E3'), and a further downstream enhancer (Ed). Previous studies on B lymphocytes derived from mutant embryonic stem cells have shown that deletion of either Ei or E3' significantly reduces Igkappa gene rearrangement, whereas the combined deletion of both Ei and E3' eliminates such recombination. Furthermore, deletion of either E3' or Ed significantly reduces rearranged Igkappa gene transcription. To determine whether the combined presence of both E3' and Ed are essential for Igkappa gene expression, we generated homozygous double knockout (DKO) mice with targeted deletions in both elements. Significantly, homozygous DKO mice were unable to generate kappa(+) B cells both in bone marrow and the periphery and exhibited surface expression almost exclusively of Iglambda-chains, despite the fact that they possessed potentially functional rearranged Igkappa genes. Compared with their single-enhancer-deleted counterparts, Igkappa loci in homozygous DKO mice exhibited dramatically reduced germline and rearranged gene transcription, lower levels of gene rearrangement and histone H3 acetylation, and markedly increased DNA methylation. This contributed to a partial developmental block at the pre-B cell stage of development. We conclude that the two downstream enhancers are essential in Igkappa gene expression and that Ei in homozygous DKO mice is incapable of triggering Igkappa gene transcription. Furthermore, these results reveal unexpected compensatory roles for Ed in E3' knockout mice in triggering germline transcription and Vkappa gene rearrangements to both Jkappa and RS elements. |
