| First Author | Zeng X | Year | 2020 |
| Journal | Exp Mol Med | Volume | 52 |
| Issue | 4 | Pages | 682-690 |
| PubMed ID | 32321991 | Mgi Jnum | J:356100 |
| Mgi Id | MGI:7762192 | Doi | 10.1038/s12276-020-0425-x |
| Citation | Zeng X, et al. (2020) The interdependence of mammary-specific super-enhancers and their native promoters facilitates gene activation during pregnancy. Exp Mol Med 52(4):682-690 |
| abstractText | 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. |
