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. Author manuscript; available in PMC: 2017 Sep 1.
Published in final edited form as: Nature. 2017 Mar 1;543(7644):270–274. doi: 10.1038/nature21688

Figure 2. ENL degradation induces growth arrest and transcription defects genome-wide.

Figure 2

(a) Chemical structure of dTAG-13.

(b) Kinetic evaluation of ENL-FKBP12F36V degradation in MV4;11 (Cas9+, ENL-FKBP12F36V-HA+) cells.

(c) Quantification of protein abundance following a 3 hour dTAG-13 treatment (500 nM) in MV4;11 (Cas9+, ENL-FKBP12F36V-HA+, ENL−/−) cells for proteins with 3 or more quantified spectral counts, n = 3.

(d) DMSO-normalized cellular viability in MV4;11 (Cas9+, ENL-FKBP12F36V-HA+) cells after 72-hour treatment with dTAG-13 approximated by ATP-lite assay. Mean ± s.d., n = 4.

(e) Cell cycle analysis with DMSO or dTAG-13 (500 nM) treatment by BrdU incorporation. Mean ± s.d., n = 3.

(f) Heat map representation of DMSO-normalized fold changes in cell-count normalized gene expression values caused by dTAG-13 (500 nM).

(g) Volcano plot of data shown in (f). P-value derived from two-tailed Student’s t-test, n = 3.

(h) Meta gene representation of cell-count normalized ChIP-seq (ChIP-Rx) of RNA Pol II at active genes following DMSO or dTAG-13 (500 nM) treatment for 24 hours. TSS, Transcription start site; TTR, transcription termination region.

(i) Cumulative distribution plot of RNA Pol II traveling ratios from data shown in (h).