Fig. 8: CMs are sensitive to BETis and resemble super-enhancers.
From: Context transcription factors establish cooperative environments and mediate enhancer communication
a, The log2(FC) in expression after JQ1 treatment of MEC1 cells, comparing genes controlled by LOCAL-lead (n = 1,549) and CM-lead (n = 1,249) enhancers to all other genes (n = 19,459). Enhancer–gene mapping based on closest TSS. Schematics indicate the expected sensitivity to JQ1 (lightning symbol size). Mann–Whitney test (top, P = 2.4 × 10−3, P = 1.9 × 10−10 and bottom, P = 6.1 × 10−3). b, As in a but using enhancer and gene annotations from the SEA62 (H3K27ac enhancer, n = 14,511; active enhancers (active E), n = 7,713 and super-enhancers (SE), n = 1087). Mann–Whitney test; P ≤ 2.2 × 10−16, P = 8.0 × 10−11. c, Overlap between different caQTL and no-effect enhancers with active B cell enhancers (actEs; cyan) and independent/CM pairs and no-effect–neighbor pairs with SEs (orange). Nonoverlapping enhancers are indicated in gray. d, As in a and b but splitting active E based on their LOCAL-lead/CM-lead annotation and SEs based on their independent-pair or CM-pair label (all enhancers, n = 14,511; actE, n = 6,935; LOCAL_actE, n = 378; CM_actE, n = 360; SE, n = 818; LOCAL_SE, n = 82 and CM_SE, n = 55). Significance assessed with respect to all or active E genes using a Mann–Whitney test (top—P ≤ 2.2 × 10−16, P = 2.8 × 10−5, P = 2.3 × 10−8, P < 2.2 × 10−16, P = 6.3 × 10−3 and P = 3.4 × 10−4; bottom—P ≤ 2.2 × 10−16, P = 0.15, P = 2.2 × 10−3, P = 2.3 × 10−7, P = 0.13 and P = 7.6 × 10−3). e, Summary figure. Different types of enhancers form as a function of the TF class (middle). Accessibility-associated TF classes establish accessible yet independently bound enhancers with low local TF concentration (type 1, for example, LOCAL neighbor). The addition of context-initiator TFBSs can lead to cell type-specific activation (link to H3K27ac; type 2). Context-only TFBSs boost cooperativity (BRD4 retention), leading to high-concentration regulatory factor clusters (type 3, for example, caQTL leads). caQTL lead enhancers split based on the identity of nearby elements into CM-forming (right-hand side) elements or those that only act locally (left-hand side). Lightning symbol size and shading indicate the sensitivity of enhancers to JQ1. In a, b and d, box plots denote the 25th percentile, median and 75th percentile, with whiskers extending to 1.5× the interquartile range. **P < 0.01, ***P < 0.001, and ****P < 0.0001.
