Extended Data Fig. 8: Halting loop extrusion enriches for interchromosomal interactions and reduces nuclear volume.
From: Nuclear morphology is shaped by loop-extrusion programs
a, Proportions of interchromosomal contacts detected for NIPBL-FKBP12F36V-EYFP cells cultured in the presence versus absence of dTAG-13 are shown (see Methods). b, Table depicts the frequency of interchromosomal interactions enriched in NIPBL-depleted cells. Log2 FC > 3.52 (Z-score > 2.576 with two-sided P = 0.01). c, Heat map shows clustering of interacting chromosomes normalized for size. d, Log2 fold change of transcripts abundance associated with A-A, B-B and A-B compartmental domains at interchromosomal interaction hubs in NIPBL-depleted cells. Z-score>1.96. In each box, the upper edge, horizontal centre line and lower edge represent the 75th percentile, median and 25th percentile, respectively. The upper whiskers represent the 75th percentile + 1.5× the IQR. The lower whiskers represent the 25th percentile - 1.5× the IQR. e, Volcano plot shows the differential expression of 3,951 genes located at interchromosomal hubs that were enriched in NIPBL-FKBP12F36V-EYFP cells cultured in the presence versus absence of dTAG-13. f, GO enrichment analysis for genes located at interchromosomal contact hubs that were enriched in NIPBL-FKBP12F36V-EYFP cells cultured in the presence versus absence of dTAG-13. g, Heat maps show KR-normalized interchromosomal interactions (100 kbp resolution) involving chromosomes 2 and 17 for indicated cell types and culture conditions. Bottom, genome browser (IGV) tracks depicting RNA-seq and ATAC-seq reads at genomic regions of interchromosomal hubs involving chromosomes 2 and 17. h,i, Transcription factor motif analysis of gained (h) and lost (i) ATAC-seq peaks associated with gained interchromosomal interaction hubs enriched in NIPBL-depleted cells. j, Depletion of NIPBL reduces nuclear volume in ECOMG progenitors. Plots show nuclear volumes (μm3) measured for NIPBL-FKBP12F36V-EYFP cells cultured in the presence (n = 33 cells) versus absence (n = 30 cells) of dTAG-13. Unpaired t-test was performed (P < 0.0001).
