Journal: Science (New York, N.Y.)

Article Title: The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity *

doi: 10.1126/science.aaf1644

Figure Lengend Snippet: A. Venn diagrams showing the percentage of genes upregulated (Up) or downregulated (Down) in SSEA1+ cells compared to SSEA1- cells that are affected by H1.0 knockdown (See also Table S4). The significance of the overlap is indicated (hypergeometric test). B. Oncogenic gene signatures positively correlating with DOX samples. NES: normalized enrichment score, NOM p-val: nominal p-value, FDR q-val: false discovery rate q-value. Blue: stem cell-related gene signatures. C. GSEA plots of positional gene sets positively (CHR4Q21) or negatively (CHR19P13) correlating with DOX samples. D-E. Smoothed log2 fold change of gene expression between DOX and NT (D) or washDOX and DOX samples (E) (shH1.0-1) along the human genome. Similar plots were obtained with shH1.0-2. Numbers indicate the chromosomes delimited with vertical lines. Only expressed genes (TPM > 0) are plotted. Blue: upregulated domains, red: downregulated domains. F. Distribution of GC content in RefSeq genes (all) and in the subsets of upregulated (Up) or downregulated (Down) DEGs. P-value from Student t-test.

Article Snippet: Gene set enrichment analysis (GSEA) was performed using GSEA software (version 2.1.0, Broad Institute).

Techniques: Knockdown, Gene Expression

Journal: Science (New York, N.Y.)

Article Title: The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity *

doi: 10.1126/science.aaf1644

Figure Lengend Snippet: A. Average peak density profiles of H3K4me3 and H3K27me3 centered on H1.0 binding sites. B. Correlation between H1.0 peak density and DNA GC content. The best fit line of the experimental values for GC content > 0.4, the correlation coefficient R and statistical accuracy of the fit are indicated. C. H1.0 peak density along chromosome 3. The approximate location of cytogenetic bands, upregulated (Up) or downregulated (Down) positional gene sets identified by GSEA and the corresponding DNA GC content are shown. D-F, H. Comparison between genes upregulated (Up) or downregulated (Down) in response to H1.0 knock-down, with respect to the indicated features. Smoothed average density profile of H1.0 peaks (F) and FAIRE peaks (H) show enrichment of H1.0 and increased FAIRE signal (decreased nucleosome occupancy) upon H1.0 knock-down around the transcriptional start site (TSS) of upregulated genes. RefSeq genes (All) are shown as reference. P-value from paired t-test, with Benjamini-Hochberg adjustment for F and H. G. Heatmap showing tag density of H1.0 ChIP-seq around the TSS of genes upregulated upon H1.0 knock-down. Each line represents a gene. I. Relative abundance of the indicated types of FAIRE peaks in GC-rich and AT-rich domains. Nucleosome occupancy corresponding to the different types of FAIRE peaks is schematized next to the legend. Black line: DNA, gray circles: nucleosomes. Results from shH1.0-1 are shown. Similar results were obtained with shH1.0-2. P-value from Fisher's exact test for constitutive peaks. J. Average DNA GC content centered on FAIRE peaks that appear or disappear upon H1.0 knock-down. See also Fig. S14D. P-value from paired t-test with Benjamini-Hochberg adjustment. Grey area: 95% confidence interval of the best fit after smoothing. K. Number of upregulated or downregulated H1.0-sensitive genes showing altered acetylated or methylated H3K27 at TSS upon H1.0 knockdown. Differences are not significant (n.s., Fisher's exact test).

Article Snippet: Gene set enrichment analysis (GSEA) was performed using GSEA software (version 2.1.0, Broad Institute).

Techniques: Binding Assay, Comparison, Knockdown, ChIP-sequencing, Methylation