Loop extrusion promotes an alternate pathway for isotype switching.

ABSTRACT: Class-switch recombination (CSR) involves replacement of the Cμ constant region with another downstream C_H 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 Eμ and 3'Eα enhancers that jointly anchor a chromatin loop. We report that asymmetric loop extrusion allows 3'Eα to track along the locus and form Pr-Pr-E interactions that mediate CSR between downstream S regions, followed by switching to donor Sμ. 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

SUBMITTER: Shen HM 

PROVIDER: S-EPMC8979556 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature