Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/− Mouse, a Model of Cornelia de Lange Syndrome
Figure 8
Position-specific effects on beta protocadherin (Pcdhb) expression.
(A) The protocadherin beta (Pcdhb) locus consists of 22 tandemly-oriented, single-exon genes distributed over ∼250 kb of chromosome 18. The names of genes that displayed significant reductions in expression in microarray analyses of Nipbl+/− E13.5 brain, and Nipbl+/− MEFs, are circled in red, and green, respectively. (B) Quantitative RT-PCR was used to measure the levels of 14 Pcdhb transcripts in RNA from E17.5 wildtype and Nipbl+/− brain. Data are averages from 6 wildtype and 7 mutant samples, presented as percent change from wildtype. (C) Sensitivities of gene expression to Nipbl level. Quantitative RT-PCR results for the Pcdhb transcripts in (B) were correlated with the levels of Nipbl in each mutant and wildtype sample to produce a best-fit regression line that estimates the fold-change in Pcdhb transcript per fold-change in Nipbl. Error bars representing the standard error of this estimate were obtained from the 67% confidence intervals for the slopes of the regression lines (roughly equivalent to one standard deviation; see Figure S4 for details). Sensitivities and error bars were plotted on an abscissa corresponding to the location of the transcriptional start sites of each of the Pcdhb genes. The dashed line is a smooth polynomial fit to the data. Note that a sensitivity of unity simply means that a Pcdhb transcript level varies linearly with Nipbl levels, whereas a sensitivity of 0.2 means it varies with the 1/5th power of Nipbl levels (i.e. very weakly). The data imply that sensitivity is high at both ends of the Pcdhb cluster, falling to much lower levels in the middle.