Reactivation of developmentally silenced globin genes through forced linear recruitment of remote enhancers.

ABSTRACT:

Abstract

The human genome contains regulatory DNA elements, known as enhancers, that can activate gene transcription over long chromosomal distances. Here, we showed that enhancer distance can be critical for gene silencing. We demonstrated that linear recruitment of the normally distal strong HBB enhancer to developmentally silenced embryonic HBE or fetal HBG promoters through deletion or inversion of intervening DNA sequences led to strongly reactivated expression in adult erythroid cells and ex vivo differentiated hematopoietic stem and progenitor cells. A similar observation was made for the HBA locus in which deletion-to-recruit of the distal enhancer strongly reactivated embryonic HBZ expression. Overall, our work assigned function to seemingly nonregulatory genomic segments;

SUBMITTER: Felder AK 

PROVIDER: S-EPMC12824704 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature