|
KMID : 0620920200520040013
|
|
Experimental & Molecular Medicine
2020 Volume.52 No. 4 p.13 ~ p.13
|
|
|
The interdependence of mammary-specific super-enhancers and their native promoters facilitates gene activation during pregnancy
|
|
Zeng Xianke
Lee Hye-Kyung
Wang Chaochen
Achikeh Precious
Liu Chengyu
Hennighausen Lothar
|
|
|
Abstract
|
|
|
|
Lineage-specific genetic programs rely on cell-restricted super-enhancers, which are platforms for high-density transcription factor occupation. It is not known whether super-enhancers synergize specifically with their native promoters or provide autonomous and independent regulatory platforms. Here, we investigated the ability of the mammary Wap super-enhancer to activate the promoter of the juxtaposed and ubiquitously expressed Tbrg4 gene in the mouse mammary gland. The Wap super-enhancer was fused, alone or in combination with the Wap promoter, to the Tbrg4 gene. While the super-enhancer increased the expression of the Tbrg4 promoter five-fold, the combination of the super-enhancer and promoter resulted in 80-fold gene upregulation, demonstrating lineage-specific promoter?enhancer synergy. Employing ChIP-seq profiling to determine transcription factor binding and identify activating histone marks, we uncovered a chromatin platform that enables the high-level expression of the native promoter?enhancer but not the heterologous promoter. Taken together, our data reveal that lineage-specific enhancer?promoter synergy is critical for mammary gene regulation during pregnancy and lactation.
|
|
|
KEYWORD
|
|
|
Gene regulation, Next-generation sequencing
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|