High-Resolution HP1-Binding Profiles

<p>(A and B) Maps of Chromosome 2, (C) Chromosome 4, (D) pericentric <i>light</i> gene, (E) pericentric <i>concertina</i> gene, and (F) cytological region 31. Inset in (A) shows a more detailed view of the centromere-proximal 0.4 Mb of 2L. Each stick represents the mean HP1–Dam/Dam binding ratio of a single GATC fragment, for one representative experiment. Fragments significantly bound by HP1 are marked in red, fragments not significantly bound by HP1 are shown in black. Gaps originate from nonunique sequences for which binding cannot reliably be determined. Positions of genes (open rectangles) and TEs (gray rectangles) are shown in D–F. Arrows in (D) and (E) indicate orientation of the genes.</p

HP1 Binding Is Linked to H3K4me2 and Histone H3.3 Patterns

<p>Alignment of HP1-bound genes to (A) their TSSs and (B) the 3′ end of their transcription units. TSS-aligned genes include upstream regions up until the next upstream gene; 3′ end aligned genes include downstream regions until the next downstream gene. Curves show running mean (window size 100) of HP1-binding ratios (log₂) for nonpericentric (green) and pericentric target genes (blue). (C) H3K4me2 levels of TSS-aligned genes in nonpericentric regions with high (red) or low (black) levels of HP1 as defined in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030038#pgen-0030038-g002" target="_blank">Figure 2</a>. H3K4me2 levels were taken from Schubeler et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030038#pgen-0030038-b053" target="_blank">53</a>]. (D) Frequency distribution of H3K4me2 levels around the TSS (−500 to +1000 bp) for genes with high (black line) and low (gray lines) HP1 levels, either all genes (dotted gray line) or expression matched (solid gray line). (E and F) TSS alignment of H3.3 levels for genes with high (red) and low (black) HP1 levels in nonpericentric (E) and pericentric (F) regions. H3.3 data were taken from Mito et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030038#pgen-0030038-b051" target="_blank">51</a>]. In (C), (E), and (F) running mean window sizes correspond to 2% of the total number of datapoints.</p

Most HP1-Bound Genes Are Actively Transcribed

<p>Density plot (smoothed histogram) showing the distribution of normalized expression levels of (A) nonpericentric and (B) pericentric genes that are strongly bound by HP1 (high HP1, average HP1 log₂-ratio along entire gene >2 [red]) or genes with low or no binding by HP1 (low HP1, average HP1 log₂-ratio along entire gene <2 [black]). Expression data were taken from Pickersgill et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030038#pgen-0030038-b050" target="_blank">50</a>].</p

HP1 Binding to Individual Transposon Copies

<div><p>(A) Frequencies of copies of the different TE types that are target of HP1 (dark gray) in nonpericentric (top) and repeat-rich pericentric (bottom) regions. A TE copy was counted as an HP1 target if, in the unique flanking 1 kb on each side of the TE, at least one GATC fragment was significantly bound by HP1.</p><p>(B) HP1-Dam/Dam–binding ratios at unique sequences within 1 kb of a TE are plotted as a function of the FRI_20kb (see main text). Running mean with window size 20 is shown for HP1 binding as a function of the FRI_20kb (red line).</p></div

HP1 and Polycomb Form Two Distinct, Nonoverlapping Chromatin Domains That Are Often in Close Proximity to Each Other

<p>Running mean (window size 20 GATC fragments) of HP1-Dam/Dam–binding ratios (black) and Pc-Dam/Dam–binding ratios (red) of (A) Chromosome 4; (B and C) pericentric regions of Chromosome 2; and (D) a repeat-rich region on the right arm of Chromosome 2 (cytological region 42AB). Positions of genes are indicated below each graph.</p

Preferential Binding of HP1 to Exon-Dense Genes

<p>(A–C) Pie charts showing the overlap of GATC fragments with promoters (black), 5′ UTRs (green), exons (yellow), introns (white), 3′ UTR (black), and intergenic regions (blue) for all fragments represented on the high-density oligonucleotide array (top) and only those fragments that are significantly bound by HP1 (bottom). This analysis was performed for (A) all fragments, (B) nonpericentric fragments, and (C) pericentric fragments. (D and E) Density plot showing the frequency distribution of exon densities (i.e., the fraction of sequence in transcription units that consists of exons) for genes with high HP1 levels (red) and genes with low HP1 levels (black), in (D) nonpericentric and (E) pericentric genes. Only genes with a length >5 kb were included in this analysis.</p

The structural basis for cohesin-CTCF-anchored loops

Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human cohesin. We report a crystal structure of SA2–SCC1 in complex with CTCF at a resolution of 2.7 Å, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF

Boletín de la Estadística Municipal de Cuenca: - 1918 enero 1

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

Additional file 6: Table S5. of Quantitative analysis of chromatin interaction changes upon a 4.3 Mb deletion at mouse 4E2

(a) Summary of df DIRs overlap with CTCF, Mediator, and cohesin binding sites. Column 1, Region, refers to the viewpoint assessed. Column 2, diffsites, refers to df DIRs. Column 4, no. sites and feature name corresponds to the number of DIRs that contain the specified genomic feature. Column 6, bp sites feature, presents the sum of DIRs bp which contain the specified feature. Column 8, no. features, indicates the number of features included inside DIRs. Percentages in columns 5, 7, and 9 are calculated based on the total number of regions or features in the preceding column. (b) Summary of df DIRs overlap with CTCF, Mediator, and cohesin binding sites. Column 1, Region, refers to the viewpoint assessed. Column 2, diffsites, refers to df DIRs. Column 4, no. sites and feature name corresponds to the number of DIRs that contain the specified genomic feature. Column 6, bp sites feature, presents the sum of DIRs bp which contain the specified feature. Column 8, no. features, indicates the number of features included inside the DIRs. Percentages in columns 5, 7, and 9 are calculated based on the total number of regions or features in the preceding column. (c) Summary of +  D Bl6 DIRs overlap for viewpoints 1, 2, 11, and 12 with CTCF, Mediator, and Smc1 binding sites. Column identities are as described in (a). (d) Summary of Monte Carlo simulations for assessing statistical significance of protein binding overlaps for +  D Bl6 DIRs for viewpoints 1, 2, 11, and 12. Column identities are as described in (b). Notice the significant p-values obtained for CTCF and Smc1 binding (p-val < 0.001, rounded down to zero in table). (XLSX 31 kb

Boletín de Segovia: Número 116 - 1868 septiembre 25

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200