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Fig. 1 | Clinical Epigenetics

Fig. 1

From: BET bromodomain inhibitors PFI-1 and JQ1 are identified in an epigenetic compound screen to enhance C9ORF72 gene expression and shown to ameliorate C9ORF72-associated pathological and behavioral abnormalities in a C9ALS/FTD model

Fig. 1

Bromodomain inhibitors enhance C9ORFF72 gene promoter-driven expression in the SH-SY5Y LE90 G4C2 reporter cell line. a Schematic representation of the two SH-SY5Y cell lines stably expressing a segment of the human C9ORF72 gene, including the promoter region and exons 1a through 2, driving the expression of a luciferase reporter gene. Between exons 1a and 1b, increasing G4C2 hexanucleotide repeat expansions (red hexagons) were inserted: 10 (SH-SY5Y WT) or 90 (SH-SY5Y LE90). b Quantification of the basal luciferase activity in each cell line. Values were normalized to total protein concentration and displayed as relative luciferase unit (RLU). Bars represent mean ± S.E.M. ***P < 0.001 relative to SH-SY5Y WT cells, unpaired Student’s t-test (n = 3 independent experiments). c Quantification of luciferase activity at the SH-SY5Y LE90 cells following an incubation for 24 h with 14 selective small molecule inhibitors targeting bromodomains (green bars), histone methyltransferase EZH2 (blue bars), chromodomains (brown bars), the histone demethylase LSD1 (red bar) and the histone acetyltransferase p300 (orange bar). As a control, SH-SY5Y LE90 cells were also treated with 0.05% (v/v) DMSO (white bar), the same concentration used as the vehicle for most of the epidrugs. Luciferase activity in the treated SH-SY5Y LE90 cells was normalized to untreated SH-SY5Y LE90 cells (black bar). Bars represent mean ± S.E.M. ***P < 0.001 relative to DMSO, or ###P < 0.001 relative to Untreated, one-way ANOVA (n = 3 independent experiments)

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