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Testing the super-enhancer concept

Many enhancers exist as clusters in the genome, which has led to the coining of the term ‘super-enhancer’. In this Viewpoint, five experts discuss our biological understanding of enhancer clusters, how we can responsibly study their functions, and their opinions on whether names for enhancer clusters are an informative reflection of their functional properties. They also provide their thoughts on key unanswered questions and future directions in the field.

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Authors and Affiliations



Gerd A. Blobel holds the Frank E. Weise III Endowed Chair in Paediatric Hematology at the Children’s Hospital of Philadelphia and the Perelman School of Medicine. He is the co-director of the Epigenetics Institute at the University of Pennsylvania. Dr Blobel earned his MD degree from the University of Heidelberg, Germany, and a PhD degree from Rockefeller University in New York. His laboratory studies nuclear architecture, and the genetic and epigenetic control of gene expression.

Douglas R. Higgs (FRS) qualified in Medicine at King’s College Hospital Medical School in 1974 and trained as a haematologist. Until early 2020, he was Director of the MRC Molecular Haematology Unit and Director of the MRC Weatherall Institute of Molecular Medicine. He is now Emeritus Professor of Haematology at the University of Oxford and his laboratory is currently focusing on understanding how genes are regulated during haematopoiesis.

Jennifer A. Mitchell is a professor in Cell and Systems Biology at the University of Toronto, Canada. She received her PhD from the University of Toronto and completed postdoctoral studies in the laboratory of Peter Fraser at the Babraham Institute in Cambridge, UK. Her laboratory investigates transcriptional mechanisms regulating pluripotency and lineage commitment.

Dimple Notani is an Assistant Professor at the National Centre for Biological Sciences in Bangalore, India. She is an EMBO Global Investigator and a Wellcome-DBT India Alliance Fellow. Her group uses an interdisciplinary approach to understand the dynamic interplay between chromatin organization, regulatory elements and non-coding RNAs in gene regulation.

Richard A. Young is a professor at the Whitehead Institute and Massachusetts Institute of Technology (MIT). Dr Young studies gene regulation in health and disease. He has served as an adviser to the World Health Organization, the National Institutes of Health and numerous scientific societies and journals. Dr Young’s honours include Membership in the National Academy of Sciences and the National Academy of Medicine, and Scientific American has recognized him as one of the top 50 leaders in science, technology and business. He has founded and advised companies in the biotechnology and pharmaceutical industry, and currently serves on the boards of Syros Pharmaceuticals, CAMP4 Therapeutics, Omega Therapeutics and Dewpoint Therapeutics.

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Correspondence to Gerd A. Blobel, Douglas R. Higgs, Jennifer A. Mitchell, Dimple Notani or Richard A. Young.

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Competing interests

R.A.Y. is a founder and shareholder of Syros Pharmaceuticals, CAMP4 Therapeutics, Omega Therapeutics and Dewpoint Therapeutics. G.A.B., D.R.H., D.N. and J.A.M. declare no competing interests.

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Blobel, G.A., Higgs, D.R., Mitchell, J.A. et al. Testing the super-enhancer concept. Nat Rev Genet 22, 749–755 (2021).

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