| First Author | Shen HM | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 8 | Pages | 110059 |
| PubMed ID | 34818547 | Mgi Jnum | J:334662 |
| Mgi Id | MGI:6883790 | Doi | 10.1016/j.celrep.2021.110059 |
| Citation | Shen HM, et al. (2021) Loop extrusion promotes an alternate pathway for isotype switching. Cell Rep 37(8):110059 |
| abstractText | Class-switch recombination (CSR) involves replacement of the Cmu constant region with another downstream CH region. CSR is initiated by activation-induced cytidine deaminase (AID)-mediated DNA breaks that are targeted to transcriptionally active switch (S) regions. S region promoters (Prs) direct synapsis by associating with the Emu and 3'Ealpha enhancers that jointly anchor a chromatin loop. We report that asymmetric loop extrusion allows 3'Ealpha to track along the locus and form Pr-Pr-E interactions that mediate CSR between downstream S regions, followed by switching to donor Smu. This alternative pathway bypasses sequential switching and creates immunoglobulin (Ig)E(+) B cells in the absence of IgG1 expression. Based on the analysis of diagnostic CSR products in B cell subsets, we identify a BCR-negative cell intermediate that is pivotal to efficient CSR. |
