Fig. 2: Chromatin domains rearrange extensively in brain cells, notably at long genes that undergo melting events.
From: Cell-type specialization is encoded by specific chromatin topologies
a, Example of cell-type-specific contacts at genomic regions (chromosome 2: 64.3–67.3 Mb) with differential expression. Dashed boxes represent 500 kb insulation scores used to determine TAD boundaries (indicated with coloured boxes below). Replicate 1 is shown for brain cells. b, UpSet plots representing multiway TAD boundary comparisons show extensive cell-type specificity. Boundaries were defined as 150 kb genomic regions centred on the lowest insulation score windows and were considered different when separated by >50 kb edge-to-edge. c, Cell-type-specific borders contain genes with GO terms relevant for cell functions. The top four GO terms were the most enriched, and the fifth was selected (over-representation measured by Z-score; one-sided Fisher’s exact permuted P values < 0.01). Asterisk indicates multiple Hist1 genes. d, e, Grik2 and Dscam overlap with cell-type-specific TAD borders and extensively decondense, or ‘melt’, in PGNs and DNs, respectively. f, The MELTRON pipeline was applied at long genes (>300 kb, 479 genes) to determine melting scores from contact density maps that represent insulation score values using 100–1,000 kb squares. Genes were considered to melt if the melting score computed across their coding region was >5 (P < 1 × 10−5; one-sided Kolmogorov–Smirnov testing using maximum distances between distributions). g, Melting associates with higher expression, especially in PGNs and DNs (two-sided Wilcoxon rank-sum test; **P < 0.01, ****P < 0.0001; P values from left to right, P = 3.5 × 10−3, P = 1.8 × 10−8, P = 8.3 × 10−6). lsRRPM, length-scaled RNA reads per million; RPM, reads per million.
