Fig. 5: mH2A2 is a negative regulator of estrogen targets.

a Transcription factors and DNA-binding molecules whose binding sites as defined by ChIP-seq peaks from ReMap data for MCF7 cells are significantly enriched (Benjamini-Hotchberg corrected p-value < 0.05) at CRE sites from each CRE class of MCF7 cells (enrichment statistics computed using ReMapEnrich). Effect size is defined as the log (base 10) ratio between the observed and expected number of overlaps. Molecules are ranked by enrichment in mBE. b Representative images of MCF7 spheroids. Scale bar, 500 µm. c Growth ratio of MCF7 3D spheroids after treatment with EtOH and E2 (Estradiol) in microwells after 7 days. Scatter plot of area factored with GFP Intensity Density in individual spheroids. Horizontal bars signify mean values +/− SE (left). Unpaired (two-tailed) student’s t-test *p < 0.05, **p < 0.005. d Violin plots showing the number of cut sites (per million bases) overlapping the five classes of CRE in MCF7 wt and mH2A2KO clones. The number of datapoints, n, equals the number of CRE per class shown in Fig. 1c. e Cohen’s effect size distributions of TF binding sites in mH2A2KO cells compared to wt MCF7 cells, grouped by binding sites found in estrogen- or control-specific cell lines (or both). f Circos chord diagram (left) showing the distribution of interactions between CREs that belong to each pair of CRE classes in MCF7 wt and mH2A2KO cells. Interactions were predicted using Cicero on scATAC-seq data using a threshold of co-accessibility score > 0.1. The width of each chord represents the number of interactions between CRE of each pair of classes. Lighter colors are used to represent wt counts and darker colors to represent mH2A2KO counts. The fold change of number of interactions per interaction type in mH2A2KO over those in wt are shown as a bar plot (right).