Hormones boost gene activity through super enhancers



It is well established that pregnancy hormones activate genetic programs that control the development of mammary tissue and the production of milk to nourish the young. However, the molecular mechanisms that activate genes during pregnancy by up to 1,000-fold were unknown.


IRP researchers, led by Lothar Hennighausen, Ph.D., discovered mammary-specific super enhancers that responded to pregnancy hormones by activating specific gene sets. By using CRISPR/Cas9 gene editing technology they dissected, for the first time, a complex super-enhancer and discovered a functional hierarchy among its individual constituent components.


Super enhancers, or stretch enhancers, have previously been defined by their structure but evidence of their functional significance within a living organism has been lacking. For the first time ever, this study used genome editing in a mouse model to define the biological role of super-enhancers, and the discovery of hierarchies within these enhancers points to a higher level of complexity than had originally been anticipated.


Shin HY, Willi M, HyunYoo K, Zeng X, Wang C, Metser G, Hennighausen L. (2016). Hierarchy within the mammary STAT5-driven Wap super-enhancer. Nat Genet. 48(8): 904-911.