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Researchers from Oxford University & New York University have revealed how super-enhancers work to increase gene expression of the α-globin gene.

Every cell in our bodies contains DNA encoding our genes. Genes are the instructions for the cell to create new proteins which complete the functions of the cell to keep it healthy, dividing and metabolising. However, not all our genes can be switched on at the same time or the cell would be overwhelmed. Regulation of genes is a complex area of biology which we know involves enhancers and transcription factors, but the specifics of most processes is still a mystery.

Now though, group leaders of the laboratory of Gene Regulation Dr Mira Kassouf (MRC Weatherall Institute of Molecular Medicine (WIMM)) & Prof. Doug Higgs (MRC WIMM & CAMS-Oxford Institute Principal Investigator) have uncovered the mystery of the endogenous multipartite α-globin super-enhancer. α-globin is a component (subunit) of a larger protein called haemoglobin, which is the part of red blood cells responsible for carrying oxygen to cells and tissues throughout the body.

Enhancers control expression of key genes associated with the identity of the cell, i.e. whether the cell becomes a blood, brain, or liver cell. Super-enhancers were shown recently to be a team of two to five enhancers that work together to drive very high levels of gene expression. 

In this new paper, published in Cell, Blayney et al have discovered that each enhancer within the endogenous multipartite α-globin super-enhancer complex works together as a team in which individual elements play different roles. In this way, together, the super-enhancer is greater than the sum of its parts. They found that some elements act as classical enhancers while others have no intrinsic enhancer activity but facilitate to increase the efficiency of the enhancers. The researchers suggest that these facilitators may be required to provide the information that joins the enhancers to the genes they control and thereby may help direct the enhancer to its rightful target gene. 

Read the full article "Super-enhancers include classical enhancers and facilitators to fully activate gene expression" here.