Fig. 1

Global decrease of cohesin binding to chromatin in Nipbl heterozygous mutant MEFs. a Cohesin-binding sites identified by ChIP-sequencing using antibody specific for Rad21 in control wild type and Nipbl+/− MEFs. Peak calling was done using AREM [50]. The p value and FDR are shown. b Heatmap comparison of Rad21 ChIP-seq data with those of SMC1, SMC3, SA1, and SA2. Rad21 peaks in the wild type MEFs are ranked by strongest to weakest and compared to the ChIP-seq data of SMC1, SMC3, SA1, and SA2 in MEFs (GSE32320) [67] in the corresponding regions. The normalized (reads per million) tag densities in a 4-kb window around each Rad21 peak are plotted, with peaks sorted from the highest number of tags in the wild type MEFs to the lowest. c Histogram of cohesin peak widths in wild type and mutant MEFs, indicating the number of peaks in a given size range. The segmentation of the histogram is at 100 bp intervals. The median value is indicated with a vertical black line and labeled. d Scatter plot of histone H3 ChIP-seq tag counts in wild type and mutant MEFs in 500 bp bins across the mouse genome. The values are plotted in log reads per million (RPM). e Histogram showing the distribution of total peaks called. A comparable number of reads to the Nipbl+/− mutant dataset (i.e., 4,740,463) were sub-sampled from the wild type dataset, and peaks called using only the sub-sampled reads. This process was performed 1000 times to produce the histogram above. Mean values with standard deviations are shown. f Heatmap analysis of cohesin binding in wild type (WT) MEFs and corresponding peak signals in Nipbl+/− MEFs. The normalized (reads per million) tag densities in a 4-kb window around each peak are plotted, with peaks sorted from the highest number of tags in the wild type to the lowest. Peaks are separated into two categories, those that are found only in wild type (“WT only”) and those that overlap between wild type and Nipbl+/− (“common”). Preimmune IgG ChIP-seq signals in the corresponding regions are also shown as a control. The color scale indicates the number of tags in a given region. g Histogram of the ratio between normalized (reads per million total reads) wild type and mutant reads in peaks common to both. Positive values indicate more wild type tags. The black line indicates the mean ratio between wild type and mutant tag counts