Interplay between CTCF-binding and CTCF-lacking regulatory elements in generating an architectural stripe at the Igh locus.

ABSTRACT: Three-dimensional genome organization orchestrates recombination and transcription of immunoglobulin heavy chain (Igh) genes. The structure of wild-type (WT) alleles includes a prominent architectural stripe that extends from a cluster of CTCF binding elements at the 3' end of the locus (3'CBE), suggesting interactions of this end with sequences throughout the 2 Mb Igh TAD. Here we elucidate interplay between regulatory elements located in the 3'Igh domain (260 kb) that impact the stripe. The CTCF-lacking intronic enhancer, Eµ, promotes stripe formation and tethers sub-TADs between flanking CTCF-bound 3'CBE and IGCR1. Substituting Eµ with an EF1α promoter in different orientations partially recapitulates epigenetic features of WT Igh alleles, including active histone modifications, sub-TAD

SUBMITTER: Ma F 

PROVIDER: S-EPMC11876664 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature