(A) Bottom, schematic of ENL protein structure. The mutated regions are in purple. IDR, intrinsically disordered region. AHD, ANC1 homologue domain. Top, protein sequences for ENL WT and mutant (T1-T8).
(B-D) Representative images (B) and quantification in HEK293 cells transfected with indicated mCherry-ENL constructs. B, all cells shown had similar mCherry-ENL intensities. C, plot showing puncta formation and mCherry intensities. Boxes highlight the top 25% highest mCherry-ENL levels among cells without detectable puncta. D, fraction of in-puncta fluorescence intensity as a function of mean nuclear intensity. Each dot indicates one cell (n at the range of 49~78).
(E) Representative images and quantification of in vitro droplet formation by indicated ENL(FL) constructs (375 nM).
(F) Western blotting showing near endogenous levels of WT and mutant Flag-ENL transgenes in HEK293 cells. V, empty vector.
(G-I) Flag IF staining (G) and quantification (H and I) in HEK293 cells. H, percentage of nuclei with and without Flag-ENL puncta. I, the number of puncta in each nucleus. Center lines indicate median and box limits are set to the 25th and 75th percentiles. H and I: cell number at the range of 32~49.
(J) IF staining of Flag-ENL (green) and H3K27ac (magenta) in HEK293 cells. The enrichment of H3K27ac at ENL puncta (magenta line) and random sites (gray line) was quantified. T1, n = 28 cells; T1(Y78A), n = 26 cells.
(K) Representative images (K) and quantification (L) showing co-localization of Halo-ENL-T1 puncta with HOXA11 nascent RNA FISH foci (n = 20 cells).
(M and N) ChIP-qPCR analysis of Flag-ENL occupancy at the HOXA locus (M) and mRNA expression (normalized to GAPDH) of HOXA genes (N) in HEK293 cells expressing endogenous levels of indicated Flag-ENL transgenes.
H and L: Chi-square test. E, I, M, N: two-tailed unpaired Student’s t-test. *** P < 0.001. E, M, N
Data represent Mean ± S.D.
See also Figures S1 and S2.