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. 2013 Mar 25;110(15):6037–6042. doi: 10.1073/pnas.1215145110

Fig. 1.

Fig. 1.

Placenta has PMDs covering tissue-specific genes. (A) Methylation levels across the long arm of chromosome 21 in five noncultured human tissues and the H9 hESC line. Smoothing was done using a kernel smoother. (B) The distribution of average percent methylation across 20-kb windows tiling all autosomes. (C) Violin plots showing distribution of methylation levels from four different individuals in HMD and PMD regions from all autosomes on the Infinium 450K array. (D) Representative example on 21q of hidden Markov model-derived PMDs maps (top black bars) based on MethylC-seq data (black landscape plot). In comparison are Infinium 450K data from 21 different third-trimester placental samples (blue landscape plots) and the average of 5 first-trimester (yellow), 6 second-trimester (red), and 21 third-trimester (brown) placental samples. Promoters, CpG islands, and CpG island shores were removed from Infinium data before analysis. (E) Placental PMDs (upper left circle) were analyzed for overlap with previously described PMDs in neuronal cells (SH-SY5Y; upper right circle) and fetal lung fibroblast cells (IMR90; lower circle). These overlaps were used to define seven tissue-specific PMD subtypes: placenta-specific PMDs (P-PMD; red), neuronal-specific PMDs (N-PMD; yellow), lung-specific PMDs (L-PMD; blue), lung-specific HMDs (L-HMD; orange), neuronal-specific HMDs (N-HMD; purple), placenta-specific HMDs (P-HMD; green), and PMDs in all three tissues (all-PMD; brown). The number of genes in each domain type is shown. Tissues with higher expression of genes in L-HMDs, N-HMDs, and P-HMDs by DAVID analysis are diagrammed with arrows. These subdomains are predicted to have genes with functions specific to that tissue type. Benjamini significance values are shown. (F) GO biological process classifications for genes in each domain subtype using DAVID, color-coded as in Fig. 1E. “Sensory perception of “smell,” “neurological system process,” and “cell surface receptor signal transduction” had Benjamini P values of 1.2 × 10−265, 4.0 × 10−148, and 1.5 × 10−104, respectively.