Table 1.
Name of disease | Genetic defect | Identification of superenhancer | Disease alleviation | Refs |
---|---|---|---|---|
JIA | Superenhancer in JIA patient synovial fluid derived CD4+ memory–effector T cells | H3K27Ac ChIP | JQ1 inhibits superenhancer: reduced disease associated gene expression | 80 |
Multiple myeloma | Translocation of 3′ IgH superenhancer to MYC gene | 18-fold more mediator, 16-fold more BRD4, higher H3K27 binding | Treatment with JQ1: loss of BRD4 at superenhancers and transcription elongation defects | 78 |
Acute lymphoblastic leukemia | Introduction of binding motifs for MYB transcription factor upstream of TAL1 oncogene creating a super-enhancer | H3K27Ac ChIP | CRISPR-Cas9 deletion of enhancer region causes complete abrogation of TAL-1 expression | 79 |
Diffuse large B cell lymphoma | Enhancer-associated factor BRD4 binds to POU2AF1, BCL6, PAX5, IRF8 genes; all essential for B cell fate determination, germinal center formation. | BRD4 and confirmed with H3K27Ac | JQ1 abolishes BRD4 binding | 22 |
Cornelia de Lange syndrome | Defective NIPBL fails to facilitate looping of enhancers to promoters | 82 | ||
HD | Downregulation of genes controlled by superenhancers in HD striatum | H3K27Ac | 77 | |
RA | Half of RA risk genes in CD4+ T cells link to superenhancers | H3K27Ac | Treatment with Janus kinase inhibitor tofacitinib impacts superenhancer–gene interaction | 81 |
Abbreviations: BRD4, [CK17]; ChIP, chromatin immunoprecipitation; HD, Huntington’s disease; JIA, juvenile idiopathic arthritis; NIPBL,; RA, rheumatoid arthritis.