Extended Data Figure 10: Expression changes in ΔNipbl hepatocytes. | Nature

Extended Data Figure 10: Expression changes in ΔNipbl hepatocytes.

From: Two independent modes of chromatin organization revealed by cohesin removal

Extended Data Figure 10

a, Changes in gene expression between TAM controls and ΔNipbl liver cells (four replicates for each condition) analysed with DESeq262. Genes with significant changes in gene expression (FDR >0.05) are coloured red (upregulated, n = 487) or blue (downregulated, n = 637), with larger dots corresponding to genes with a fold-change of more than 3. b, Intergenic distances for the different categories of disregulated genes (with fold-change more than 3; upregulated, 268; downregulated, 350; unchanged, 15,055). Statistical differences determined by an unpaired two-tailed t-test. The differences between means were 50,020.40 (CI 95% = 27723.85–72316.95) and 52,185 (CI 95% = 21824–82547) for downregulated versus unchanged, and downregulated versus upregulated, respectively. c, Size distribution of the TADs observed in wild-type cells (lost in ΔNipbl cells) depending on the degree alteration of their transcriptional states. The size of TADs with transcriptional changes (red) is significantly larger than those that do not show transcriptional alterations (black) (Kolmogorov–Smirnov, P = 4.095 × 10−8). d, Change in transcription in non-genic intervals (including intergenic and antisense within gene bodies). Gene expression was calculated as the normalized number of reads within intervals defined by merging adjacent 1-kb windows showing readcounts over background (see Methods). The numbers of non-coding transcripts upregulated (in red) or downregulated (in blue) in ΔNipbl compared to the TAM control is given (P < 0.01 using a two-tailed t-test, four replicates per condition, fold-change higher than 8), with the second number indicating the high-confidence events (labelled with coloured dots, expression value over an arbitrary threshold of 30 reads) which constitute the list used for subsequent analyses. e, Comparison of control and ΔNipbl H3K27ac normalized signals within predicted liver enhancer elements (n = 51,850; readcounts within ±500 bp of predicted enhancer peak)69. fi, Examples of transcriptional changes upon Nipbl deletion. Stranded RNA-seq and ChIP–seq tracks (H3K4me3, H3K27ac) are shown for control (blue) and ΔNipbl (red) samples. Comparison of the chromatin profiles are shown with log2Nipbl/TAM] tracks for H3K4me3 and H3K27ac (in grey). Active enhancers (peaks of high H3K27ac, H3K4me1, low H3K4me3)69 are depicted as green ovals. f, Chr10: 21,090,000–21,781,000. Bidirectional transcription (position labelled with a blue bar) arises from an isolated enhancer in ΔNipbl cells. g, Chr17: 45,945,000–46,176000. Bidirectional transcription (position labelled with a blue bar) arises from two cryptic promoters (H3K4me3 peaks, no or weak transcription in TAM) downstream of Vegfa. h, Chr3: 21,712,500–22,126,240. A new transcript from a cryptic promoter 100 kb upstream of Tbl1xr1. H3K27ac signal is enhanced at peaks surrounding the activated cryptic promoter. i, Chr15: 9,873,000–10,354,700. Promoter switch for Prlr, from an upstream promoter to a more downstream one surrounded by active enhancers. j, chr6: 141,743,961–141,904,692. Downregulation of Slco1a1 and concomitant upregulation of Slco1a4 and noncoding intergenic transcripts (arrowheads). Distance of Slco1a4 promoter to intergenic enhancers is less than 10 kb, compared to 80 kb for Slco1a1.

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