Extended Data Fig. 8: Melting genes often show increased contacts with their own chromosome.
From: Cell-type specialization is encoded by specific chromatin topologies
a, Melting genes are more likely to gain intra-chromosomal contacts in PGNs and DNs R1, but not OLGs, compared to mES cells (two-sided Wilcoxon rank-sum test; **p<0.01, ***p<0.001; p-values from left to right, p = 0.003, 0.0003, 0.329). Median trans-cis contact ratios were calculated for each gene with domain melting in DNs, PGNs, or OLGs, and compared to mES cells. b, Median trans-cis contact ratios were calculated for each gene with domain melting in PGNs R2 or DNs R2. Median trans-cis ratios were significantly lower for PGNs and DNs R2 melting genes when compared to mES cells (two-sided Wilcoxon rank-sum test; *p<0.05, ***p<0.0001; p-values were p = 0.037 and 0.0003 for PGNs and DNs, respectively). c, Correlation of median trans-cis ratios for all long genes (> 300kb) in R1 and R2 for PGNs or DNs. In PGNs, median trans-cis ratios were significantly correlated between replicates, with a high correlation value (Two-sided Pearson’s R product-moment correlation; R=0.9, ****p < 2.2x10−16). DNs had a lower correlation, though the correlation was still significant (R=0.16, ***p = 0.0005). d, Median trans-cis contact ratios were calculated for each gene without domain melting. Non-melting genes show no preference for changes in trans-cis contact ratios between brain cells and mES cells (two-sided Wilcoxon rank-sum test). e, The Rbfox1 locus gains contacts with other chromosomes in PGNs, compared to mES cells. Trans-cis contact ratios were determined by the mean ratio between trans NPMI scores and cis NPMI scores (250kb genomic bins), and normalizing each ratio as a percentile for each chromosome. Inset (grey shaded region) shows a 7Mb region (Chr16: 3,000,000-10,000,000) containing the Rbfox1 gene (blue shaded region). f, Trans-cis contact ratios are shown for chromosome 12 in mES cells and DNs. Inset (grey shaded region) shows a 7Mb region (Chr12: 85,000,000-92,000,000) containing the Nrxn3 gene (green shaded region). g, Median trans-cis ratios for genes with melting domains, separated by association with NAD association (defined as > 50% of gene body with feature). For DNs, median trans-cis ratios were significantly decreased when compared to mES cells, regardless of association with NADs (two-sided Wilcoxon rank-sum test; *p<0.05, **p<0.01; p-values from left to right, p = 0.927, 0.233, 0.100, 0.010, 0.044, 0.003). For PGNs, median trans-cis ratios were significantly decreased for non-NAD associated genes (**p<0.01), and trending toward significance for NAD-associated genes, when compared to mES cells (p=0.1). OLGs had no significant differences in median trans-cis values for both NAD associated and non-associated genes, when compared to mES cells. h, Median trans-cis ratios for genes without melting domains, separated by association with NAD association (defined as > 50% of gene body with feature). NAD-associated genes had significantly lower trans-cis values in all brain cell types when compared to mES cells (two-sided Wilcoxon rank-sum test; **p<0.01; p-values from left to right, p = 0.002, 0.205, 0.013, 0.147, 0.002, 0.911). For all brain cell types, non-melting genes that were not associated with NADs had no significant differences in median trans-cis values when compared to mES cells.
