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. Author manuscript; available in PMC: 2014 Apr 11.
Published in final edited form as: Cell. 2013 Apr 11;153(2):320–334. doi: 10.1016/j.cell.2013.03.036

Figure 2. Super-Enhancers Identified in Multiple Myeloma.

Figure 2

(A) Total MED1 ChIP-seq signal in units of reads per million in enhancer regions for all enhancers in MM1.S. Enhancers are ranked by increasing MED1 ChIP-seq signal.

(B) Metagene representation of global MED1 (red line) and BRD4 (blue line) occupancy at typical enhancers and super-enhancers. The x axis shows the start and end of the enhancer (left) or super-enhancer (right) regions flanked by ±5 kb of adjacent sequence. Enhancer and super-enhancer regions on the x axis are relatively scaled. The y axis shows the average signal in units of rpm/bp.

(C) Gene tracks of MED1 (top) and BRD4 (bottom) ChIP-seq occupancy at the typical enhancer upstream of TOP1, the super-enhancer downstream of IGLL5, the typical enhancer upstream of SMARCA4, and the super-enhancer overlapping the CCND2 gene TSS. The x axis shows genomic position, and super-enhancer-containing regions are depicted with a gray box. The y axis shows signal of ChIP-seq occupancy in units of rpm/bp.

(D) Left: box plots of expression values for genes with proximal typical enhancers (white) or with proximal super-enhancers (pink). The y axis shows expression value in Log2 arbitrary units. Right: box plots of cell-type specificity values for genes with proximal typical enhancers (white) or with proximal super-enhancers (purple). The y axis shows the Z score of the Jensen-Shannon (JS) divergence statistic for genes, with higher values corresponding to a more cell-type-specific pattern of expression. Changes between expression levels are significant (two-tailed Welch's t test, p < 2 × 10−16), as are changes between cell-type-specificity levels (two-tailed Welch's t test, p = 1 × 10−14).

(E) Bar graph depicting luciferase activity of reporter constructs containing cloned fragments of typical enhancers and super-enhancers in MM1.S cells. 2 kb fragments of three super-enhancers, IGLL5, DUSP5, and SUB1, and three typical enhancers, PDHX, SERPINB8, and TOP1, ranked 1, 129, 227, 2352, 4203, and 4794, respectively, in terms of MED1 occupancy, were cloned into reporter plasmids downstream of the luciferase gene, driven by a minimal MYC promoter. Luciferase activity is represented as fold over empty vector. Error bars represent SD of triplicate experiments.

See also Figure S2 and Data S1.