The α-globin super-enhancer acts in an orientation-dependent manner

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Abstract
Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested. Here, using the α-globin locus as a model, we show that while an individual enhancer works in an orientation-independent manner, the direction of activity of a SE changes with its orientation. When the SE is inverted within its normal chromosomal context, expression of its normal targets, the α-globin genes, is severely reduced and the normally silent genes lying upstream of the α-globin locus are upregulated. These findings add to our understanding of enhancer-promoter specificity that precisely activate transcription.
Funding Information
  • RCUK | Medical Research Council (MR/N00969X/1, MR/T014067/1, MR/T014067/1, MR/T014067/1)
  • RCUK | Biotechnology and Biological Sciences Research Council (BB/Y008898/1)
  • Wellcome Trust (109097/Z/15/Z, 222843/Z/21/Z, 219979/Z/19/Z)
  • RCUK | MRC | Medical Research Foundation (MR/T014067/1)
  • Chinese Academy of Medical Sciences (2018-I2M-2-002)

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