Fig. 1

Luminescence-based screen identifies AG490 and Jaki as potential reactivators of genes on the inactive X chromosome. a Dot plot indicating the percentage of luciferase activation per drug using the Xi8 fibroblast cell line reporter for MeCP2 activation over the control (normalized values; see the “Material and methods” section). In red, we show AG490, in blue 5-Aza, and in green compounds previously reported to reactivate MeCP2 using different protocols (LY294002, OSU-03012, MLN8237, BX-912, K02288, VX-680; see the “Introduction” and the “Results” sections for more details). b Top: Chemical structure of 5-azacytidine (5-Aza), a known reactivator of MeCP2, and AG490. Bottom: Dose response of 3-day treatment of 5-Aza or AG490 in Xi8 fibroblast cells (n = 3, one representative graph shown here from three independent assays). c Left: Xi8 clone showing MeCP2 and MeCP2-luciferase genes on the inactive chromosome. Right: qRT-PCR data showing the effect of the indicated drug treatments on luciferase (Luc), Mecp2, and Xist mRNA levels; mean (± SEM) are shown, *statistical significance, p ≤ 0.05 (n = 3 per compounds, the average of three biological replicates are shown). d Left: Xa3 clone showing MeCP2 and MeCP2-luciferase genes on the active chromosome, respectively. Right: qRT-PCR data showing the effect of the indicated drug treatments on luciferase (Luc), Mecp2, and Xist mRNA levels; mean (± SEM) are shown, *statistical significance, p ≤ 0.05 (n = 3 per compounds, the average of three biological replicates are shown)