Progressing super-enhancer landscape during mammary differentiation controls tissue-specific gene regulation.

ABSTRACT: The mammary luminal lineage relies on the common cytokine-sensing transcription factor STAT5 to establish super-enhancers during pregnancy and initiate a genetic program that activates milk production. As pups grow, the greatly increasing demand for milk requires progressive differentiation of mammary cells with advancing lactation. Here we investigate how persistent hormonal exposure during lactation shapes an evolving enhancer landscape and impacts the biology of mammary cells. Employing ChIP-seq, we uncover a changing transcription factor occupancy at mammary enhancers, suggesting that their activities evolve with advancing differentiation. Using mouse genetics, we demonstrate that the functions of individual enhancers within the Wap super-enhancer evolve as lactation progresses. Most p

SUBMITTER: Lee HK 

PROVIDER: S-EPMC6237736 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature