Super-enhancers include classical enhancers and facilitators to fully activate gene expression

Super-enhancers are compound regulatory elements that control expression of key cell identity genes. They recruit high levels of tissue-specific transcription factors and co-activators such as the Mediator complex and contact target gene promoters with high frequency. Most super-enhancers contain multiple constituent regulatory elements, but it is unclear whether these elements have distinct roles in activating target gene expression. Here, by rebuilding the endogenous multipartite α-globin super-enhancer, we show that it contains bioinformatically equivalent but functionally distinct element types: classical enhancers and facilitator elements. Facilitators have no intrinsic enhancer activity, yet in their…

• WT
  Wellcome Trust

  Awards: 109097/Z/15/Z, 222843/Z/21/Z, /Z/15/Z, 215111/Z/18/Z, 219979/Z/19/Z
• UR
  UK Research and Innovation
• CA
  Chinese Academy of Medical Sciences

  Award: 2018-I2M-2-002
• NI
  National Institutes of Health
• HW
  Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University
• MR
  Medical Research Council

  Awards: MR/T014067/1, MR/T014067/1, MR/X001210/1
• NH
  National Human Genome Research Institute

  Award: RM1HG009491
• MR
  Memphis Research Consortium