Journal: Cell Reports

Article Title: Genetic Predisposition to Chronic Lymphocytic Leukemia Is Mediated by a BMF Super-Enhancer Polymorphism

doi: 10.1016/j.celrep.2016.07.053

Figure Lengend Snippet: Contact Profile of the BMF 4C Viewpoint in Combination with ChIP-Seq Data (A) Heatmap representing chromatin interactions in GM12878 cells at 40.32–40.52 Mb on chromosome 15. Chromatin contact domains called by the Arrowhead algorithm are marked by white lines ( Rao et al., 2014 ). The contact domain and CD19 + B cell super-enhancer ( Hnisz et al., 2013 ) encompassing rs539846 are labeled in pink and yellow, respectively. (B) 4C-seq analyses in MEC1 CLL cells indicate the formation of a loop domain between rs539846 and cis -regulatory elements. The 4C viewpoint (green box) lies adjacent to rs539846 (dotted line). A 10-kb masked region (gray box) is also marked. ENCODE ChIP-seq data from GM12878 cells show the correspondence between loop formation and CTCF and RELA transcription factor occupancy. Canonical transcripts and chromosome 15 position also are shown.

Article Snippet: Using 4C primer design software ( http://mnlab.uchicago.edu/4Cpd/ ), we identified a viewpoint adjacent to SNP rs539846.

Techniques: ChIP-sequencing, Labeling

Journal: Scientific Reports

Article Title: Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461

doi: 10.1038/s41598-021-88988-w

Figure Lengend Snippet: Pooled CRISPR-Cas9 screens reveal genetic determinants of sensitivity to G4 drugs. ( a ) Schematic of pooled screen. ( b ) Experimental design of drug screens. HCT116 cells were transfected with the LCV2-puro library at an MOI of 0.3. After 24 h, 0.5 µg/ml puromycin was added and the cells kept in puromycin for 3 days. On day 5 drug/vehicle treatments were started in triplicate and continued until day 19. Cells were passaged with freshly added vehicle or drugs, and harvested on days 1, 4, 5, 12, 15 and 19 to make DNA for the downstream sequencing library preparation. ( c ) Top 81 depleted genes from MAGeCK output. Each row represents the corresponding drug treatment groups. Heatmap shows the MAGeCK depletion scores of the genes. The heatmap is ordered according to the depletion scores of CX-5461 (IC 50 ) group, ranking the most depleted genes on the left. To emphasize genes with the highest depletion score, the median of the color gradient (white) was shifted to 0.2. ( d ) UpSet plot showing the intersection of candidate genes undergoing negative selection with G4 stabilizers (MAGeCK P -values < 0.045) within each drug condition. In the bottom matrix, each row represents the set of genes identified for the indicated drug condition, and each column represents the intersection of the drug condition gene sets indicated by black dots. The histogram to the right of the matrix indicates the number of genes identified for each input drug condition. The histogram on the top shows the number of genes in each intersection set. Gene hits common in all CX-5461 and PDS conditions are shown in yellow.

Article Snippet: Individual sgRNAs were designed using the Deskgen Cloud CRISPR Design Software (Desktop Genetics). sgRNA cloning into LCV2-DRX2 vector was performed as previously described , .

Techniques: CRISPR, Transfection, Sequencing, Selection