| First Author | Shin HY | Year | 2016 |
| Journal | Nat Genet | Volume | 48 |
| Issue | 8 | Pages | 904-911 |
| PubMed ID | 27376239 | Mgi Jnum | J:277922 |
| Mgi Id | MGI:6141584 | Doi | 10.1038/ng.3606 |
| Citation | Shin HY, et al. (2016) Hierarchy within the mammary STAT5-driven Wap super-enhancer. Nat Genet 48(8):904-911 |
| abstractText | Super-enhancers comprise dense transcription factor platforms highly enriched for active chromatin marks. A paucity of functional data led us to investigate the role of super-enhancers in the mammary gland, an organ characterized by exceptional gene regulatory dynamics during pregnancy. ChIP-seq analysis for the master regulator STAT5A, the glucocorticoid receptor, H3K27ac and MED1 identified 440 mammary-specific super-enhancers, half of which were associated with genes activated during pregnancy. We interrogated the Wap super-enhancer, generating mice carrying mutations in STAT5-binding sites within its constituent enhancers. Individually, the most distal site displayed the greatest enhancer activity. However, combinatorial mutation analysis showed that the 1,000-fold induction in gene expression during pregnancy relied on all enhancers. Disabling the binding sites of STAT5, NFIB and ELF5 in the proximal enhancer incapacitated the entire super-enhancer. Altogether, these data suggest a temporal and functional enhancer hierarchy. The identification of mammary-specific super-enhancers and the mechanistic exploration of the Wap locus provide insights into the regulation of cell-type-specific expression of hormone-sensing genes. |
