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Fig. 2 | Skeletal Muscle

Fig. 2

From: BET bromodomain inhibitors and agonists of the beta-2 adrenergic receptor identified in screens for compounds that inhibit DUX4 expression in FSHD muscle cells

Fig. 2

BETi have a memory effect on DUX4 that is mediated by HDACs. ac BETi cause sustained DUX4 repression. a Experimental timeline. Subconfluent MB200 FSHD2 myoblasts were treated with 1 μM of the BETi I-BET762 (I-BET) on day 0 (D0) for 8, 24, 48, or 72 h and gene expression analyzed on day 3 (D3). b DUX4 target gene mRNA levels after treatment as in a. c Expression of the myoblast lineage genes MYOD1 and MYF5 and the epigenetic modifier SMCHD1 after treatment as in a. de HDACi block the BETi-mediated memory effect. d Levels of the DUX4 target gene ZSCAN4 in MB200 FSHD2 myoblasts that were treated with the indicated compounds (DMSO control, 1 μM I-BET762, 2.5 μM MS-275, 2.5 μM MGCD0103) for 24 h and then cultured in fresh media for an additional 48 h before harvest. e ZSCAN4 expression after 72 h of continuous exposure to the indicated compounds (DMSO control, 1 μM I-BET762, 2 μM RGFP109) in MB200 FSHD2 myoblasts. Error bars indicate the standard deviation from the mean of three biological replicates. p values were calculated using a one-way analysis of variance with Dunnett’s post test. *p < 0.05

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