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1.
Figure 2

Figure 2. From: Impact of chromatin structure on sequence variability in the human genome.

Relative occurrences of indels (A) and SNPs (B) of different classes inside nucleosome core sequences and linkers. Two 50-bp linker sequences flanking the core nucleosome sequence of 147-bp in length were considered and correction for different lengths of the core nucleosome and linker sequences was performed. The 95% confidence intervals are shown with thin arrows. Dashed horizontal line corresponding to the ratio of one is shown for reference. The nucleosome type for which the data are shown is indicated above each group of bars.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.
2.
Figure 5

Figure 5. From: Impact of chromatin structure on sequence variability in the human genome.

Distribution of SNP frequencies around stable nucleosome positions in the regions that are proximal (A) and distant (B) to the TSS of human genes. TSS proximal and distant nucleosome positions were identified as those located less than 1 kb and more than 2 kb from the closest TSS respectively. Normalized profiles are shown for the positions from the combined nucleosome set (grey) and for the individual nucleosome sets: bulk (cyan), H2A.Z (blue), and H3K4me3 (red). Vertical dashed lines at zero and ±73 bp give reference of the nucleosome position and size.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.
3.
Figure 3

Figure 3. From: Impact of chromatin structure on sequence variability in the human genome.

Distribution of indels (red), SNPs (green), and stable nucleosome positions from combined set (black) around intron-exon (A) and exon-intron (B) boundaries. Zero position in each plot corresponds to the position of boundary. Exonic coordinates were taken from the USCS track RefGene that reports known protein-coding genes from the NCBI mRNA sequences collection (RefSeq)34,35. First and last exons were excluded from the analysis. Only genes for which no alternative start site was reported we considered (14,946 genes). The combined nucleosome set (‘all nucleosomes’) was used to produce this plot. The frequency profiles were calculated as described in Methods. Heatmaps shown at the bottom panels represent de-trended profiles where large-scale variations were removed.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.
4.
Figure 1

Figure 1. From: Impact of chromatin structure on sequence variability in the human genome.

Genome-wide distributions of indel and SNP events. (A,B) Distributions of indel (A) and SNP (B) frequencies around stable nucleosome positions. Results are shown for a combined set of nucleosome positions (grey) and for individual nucleosome sets: bulk (cyan), H2A.Z (blue), and H3K4me3 (red). The frequency profiles were normalized and smoothed as described in Methods. Black dashed line at position zero corresponds to the center of nucleosome position and red dashed lines at positions ±73 bp give reference of nucleosomal size. (C,D) Auto-correlation profiles for indel (C) and SNP (D) occurrences. Thin grey lines correspond to the initial profile calculated with one base-pair lag increments and thick red line represents loess smoothing of the initial data. Two local maxima in the indel profile corresponding to mono- and di-nucleosomal sizes are indicated with numbers.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.
5.
Figure 6

Figure 6. From: Impact of chromatin structure on sequence variability in the human genome.

Interplay of chromatin-mediated mutation bias and selection can shape sequence variation profile (cf. to schematic illustration in Ref. 27). (A) Bulk and epigenetically modified nucleosomes are represented with blue and red ovals. Green and orange lines represent mutation rate of SNPs and indels respectively, and black line represents selection pressure acting on the DNA sequence. (B) The significant difference in the indel rate inside and outside nucleosomes mainly determines the indel density profile observed in the genome (orange), while SNP density profile (green) is mainly affected by selection. Our results do not exclude the possibility that natural selection can affect the distribution of indels and that alteration of the mutation rate affects the distribution of SNPs. Rather, they indicate that these mechanisms are not the major factors shaping the resulting profiles.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.
6.
Figure 4

Figure 4. From: Impact of chromatin structure on sequence variability in the human genome.

Distribution of indels (red), SNPs (green), and stable nucleosome positions (black) around TSS and TES of human genes. Profiles were calculated as described in Methods. Heatmaps shown at the bottom panels represent de-trended profiles where large-scale variations were removed. (A) Profiles around TSS (position zero). The combined nucleosome set (‘all nucleosomes’) was used to produce this plot. Genes were oriented in the direction of transcription in such a way that the up-stream region is shown on the left and the downstream region is shown on the right of TSS. (B) Profiles shown separately for the frequencies of indels (dark red and orange lines) and bulk nucleosomes (black and cyan lines) for the subsets of genes associated and not associated with CpG islands at TSS. Black and cyan ovals represent nucleosomes at position +1 in CpG and non-CpG genes and are shown for a nucleosome size reference. Coordinates of CpG islands were taken from USCS genome browser annotation34. (C) Profiles computed around TES (position zero) for all genes. The combined nucleosome set was used.

Michael Y. Tolstorukov, et al. Nat Struct Mol Biol. ;18(4):510-515.

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