Fig. 2: DCM labeling and propagation in the small intestine.

a, Genome browser view of Alpi locus showing DCM-specific MeD-seq reads before and after 1 day of dox treatment (n = 3). RNA-seq (±dox, average of n = 3), POLR2A, H3K36me3 and H3K27ac ChIP-seq tracks from ENCODE are shown below. b, Scatter plot displaying RNA-seq gene expression level in relation to DCM read count per gene before (gray) and after (green) 10 days of dox induction in epithelium of jejunum. c, Gene meta-analysis showing distribution of DCM reads in the top 25%, 25–75% and bottom 25% expressed genes after 3 days of dox treatment (average plotted with ± s.e.m.). d, Pearson correlation analysis comparing DCM and ChIP-seq read count distribution. e, Experimental setup; mice received dox for 2 days with isolation of H2B-GFP_high and H2B-GFP_low and EPCAM⁺/SLC2A2⁺ cells after a 3-day chase through FACS analysis, followed by DNA isolation and MeD-seq. f, Immunocytochemistry detecting H2B-GFP (FITC) and DNA (DAPI) in jejunum of a mouse 3 days after an IP dox pulse (representative image shown from n ≥ 5 replicates; scale bar, 50 µm) g, Calculated DCM propagation rate in two independent experiments. h, Relative distribution of DCM reads in intergenic, exonic, intronic and CpG island sequences in GFP_high and GFP_low cell fractions. i, In silico prediction of DCM labeling levels after each cell division. The fold change between the simulated diluted +dox sample and background levels (−dox) are plotted. The percentage above each violin indicates the percentage of genes that can still be detected based on their estimated fold change.