Sequence, epigenetic and gene characteristics of conserved (n = 6) replication U-domain borders of H1hesc that switch from state ECi to Cj.

<p>For each border type, the table provides number (Nb), G+C content (GC), coverage by significantly enriched intervals relative to the genome average coverage for H2AZ (genome average 33%), CTCF (4.5%), NANOG (0.2%) and OCT4 (0.07%), coverage by DNase I hypersensitive sites (DHS), as well as the numbers of promoters and expressed promoters per border.</p><p>Sequence, epigenetic and gene characteristics of conserved (n = 6) replication U-domain borders of H1hesc that switch from state ECi to Cj.</p

Sequence characterictics of MRT U-domains of H1hesc and Nhdfad.

<p>(A) Density of nucleosome free regions (NFRs) with respect to the distance to the closest U-domains border specific (n = 1) to the cell line. The different colors correspond to specific U-domains of Nhdfad (black), specific U-domains of H1hesc whose border is in EC1 or EC2 (red) and specific U-domains of H1hesc whose border is in EC4 (blue). (B) Density of (NFRs) with respect to the distance to the closest conserved (n = 6) U-domains border. (C) same as (A) for the CpG o/e. (D) same as (B) for the CpG o/e. (E) same as (A) for the GC content. (F) same as (B) for the GC content.</p

(A) Cumulative distribution function (cdf) of MRT difference Δ<i>t</i> between two cell lines: Δ<i>t</i> = MRT(Nhdfad) − MRT(H1hesc) (red) and Δ<i>t</i> = MRT(Nhdfad) − MRT(K562) (black).

<p>Horizontal lines mark from bottom to top the first decile, first quartile, median, last quartile and last decile, respectively. (B) Proportion of 100 kb windows in C1+C2 blocks that have a conserved MRT (∣Δ<i>t</i>∣ < 0.2) with respect to block length: H1hesc blocks with MRT compared to Nhdfad (red) and K562 blocks with MRT compared to Nhdfad timing (black). (C) Same as (B) for C3+C4 blocks. (D) Histogram of distances to H1hesc U-domain borders for loci that have a Δ<i>t</i> = MRT(Nhdfad) − MRT(H1hesc) > 0.2 (line) and < −0.2 (dots). (E) Histogram of distances to Nhdfad U-domain borders for loci that have a Δ<i>t</i> = MRT(Nhdfad) − MRT(H1hesc) > 0.2 (line) and < −0.2 (dots). (F) Histogram of distances to K562 U-domain borders for loci that have a Δ<i>t</i> = MRT(Nhdfad) − MRT(K562) > 0.2 (line) and < −0.2 (dots).</p

Genome-wide spatial distribution of chromatin states in ESCs and differentiated cells.

<p>MRT profile along two Mb long fragments of human chromosome 5 (left) and 14 (right). U-domains are marked by an horizontal orange line and their borders by vertical red lines. Below the MRT profile, gene positions are indicated by a horizontal segment (blue: not expressed, orange: expressed) as well as the chromatin state of each 100 kb window is represented using the same color coding as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.g002" target="_blank">Fig. 2</a>. At the bottom of the plot, intervals significantly enriched in H3K27me3, H2AZ and CTCF are represented in black. At the bottom of the figure, the last panel represents the compositional skew </p><p></p><p><mi>S</mi><mo>=</mo></p><p><mi>S</mi></p><p><mi>G</mi><mi>C</mi></p><p></p><mo>+</mo><p><mi>S</mi></p><p><mi>T</mi><mi>A</mi></p><p></p><mo>=</mo><p></p><p><mi>G</mi><mo>−</mo><mi>C</mi></p><p><mi>G</mi><mo>+</mo><mi>C</mi></p><p></p><mo>+</mo><p></p><p><mi>T</mi><mo>−</mo><mi>A</mi></p><p><mi>T</mi><mo>+</mo><mi>A</mi></p><p></p><p></p><p></p> [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.ref079" target="_blank">79</a>–<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.ref082" target="_blank">82</a>] in 1 kb windows of repeat masked sequences; germline replication skew N-domains are marked by an horizontal orange line and their borders by a vertical red line.<p></p

Spearman correlation matrix between epigenetic marks in H1hesc (top) and Nhdfad (bottom).

<p>For each cell line, we computed the Spearman correlation over all 100 kb non-overlapping windows with a valid score. Spearman correlation value is color coded using the color map shown on the left. Lines for the epigenetic marks were reorganized by a hierarchical ordering using Spearman correlation distances [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.e001" target="_blank">Equation (1)</a>] as illustrated by the dendrograms on the right of the corresponding matrices. This ordering implies that highly correlated epigenetic marks are close to each other.</p

Epigenetic marks enrichment in specific MRT U-domains of H1hesc and Nhdfad.

<p>(A) Mean coverage of H2AZ enriched intervals with respect to the distance to the closest U-domain border specific to the cell line. The different colors correspond to specific U-domains of Nhdfad (black), specific U-domains of H1hesc whose border is in EC1 or EC2 (red) and specific U-domains of H1hesc whose border is in EC4 (blue). (B), (C) and (D) are as (A) for respectively CTCF, NANOG anf OCT4. Note that in (C) and (D) coverage are per thousand.</p

Mean length of chromatin state blocks per chromatin state in kb (Materials and Methods) in ES H1hesc and differentiated cells (see Table 1).

<p>Mean length of chromatin state blocks per chromatin state in kb (Materials and Methods) in ES H1hesc and differentiated cells (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.t001" target="_blank">Table 1</a>).</p

Gene content in the four prevalent chromatin states of H1hesc and K562 cell lines.

<p>For each chromatin state the following information is given: (i) the total number of promoters per chromatin state, (ii) the density of promoters per Mb, (iii) the mean level of expression per chromatin state in RPKM (Materials and Methods), (iv) the median level of expression per chromatin state in RPKM, (v) the mean gene length per chromatin state in kb.</p><p>Gene content in the four prevalent chromatin states of H1hesc and K562 cell lines.</p

Distribution of chromatin states inside replication timing U-domains of H1hesc and Nhdfad.

<p>(A) Mean coverage of chromatin states with respect to the distance to the closest U-domain border in the H1hesc cell line. (B) Mean coverage of ESC chromatin state in the 100kb window containing a U-domain border with respect to the conservation index n of the U-domain border (Materials and Methods). (A’, B’) same as (A, B) for the Nhdfad cell line. Same color coding as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003969#pcbi.1003969.g002" target="_blank">Fig. 2</a>.</p

(A) Mosaic plot representing the probabilities of transition from H1hesc chromatin states to Nhdfad chromatin states.

<p>The width of columns corresponds to the proportion of chromatin states in H1hesc. The segmentation for the <i>i</i>^<i>th</i> column follows the proportion of windows in state ECi in H1hec that become Cj in Nhdfad. In other words, if we take the first pink rectangle of the first column, its width is proportional to the probability for a 100 kb window to be in chromatin state EC1 in H1hesc and its height is proportional to the probability for a 100 kb window to be in C1 in Nhdfad given that it is in EC1 in H1hesc. The area of this rectangle (product of the previously mentioned probability) is proportional to the probability for a window to be in state EC1 in ESC and C1 in Nhdfad. (B) Same as (A) for the chromatin state changes from the cell line K562 towards Nhdfad.</p