Project description:Using ATAC-seq of the cells with cBAF-targeting gRNA or inhibitor, we identified chromatin loci whose accessibility was regulated by cBAF complex
Project description:From comparative transcriptome analysis using RNA-seq of the cells with cBAF-targeting gRNA or inhibitor, we identified the genes regulated by cBAF complex in T-ALL cell lines
Project description:Runt-related transcription factor 1 (RUNX1) is oncogenic in diverse types of leukemia and epithelial cancers where its expression is associated with poor prognosis. Current models suggest that RUNX1 cooperates with other oncogenic factors (e.g., NOTCH1, TAL1) to drive the expression of proto-oncogenes in T cell acute lymphoblastic leukemia (T-ALL) but the molecular mechanisms controlled by RUNX1 and its cooperation with other factors remain unclear. Integrative chromatin and transcriptional analysis following inhibition of RUNX1 and NOTCH1 revealed a surprisingly widespread role of RUNX1 in the establishment of global H3K27ac levels and that RUNX1 is required by NOTCH1 for cooperative transcription activation of key NOTCH1 target genes including MYC, DTX1, HES4, IL7R, and NOTCH3. Super-enhancers were preferentially sensitive to RUNX1 knockdown and RUNX1-dependent super-enhancers were disrupted following the treatment of a pan-BET inhibitor, I-BET151.
Project description:Runt-related transcription factor 1 (RUNX1) is oncogenic in diverse types of leukemia and epithelial cancers where its expression is associated with poor prognosis. Current models suggest that RUNX1 cooperates with other oncogenic factors (e.g., NOTCH1, TAL1) to drive the expression of proto-oncogenes in T cell acute lymphoblastic leukemia (T-ALL) but the molecular mechanisms controlled by RUNX1 and its cooperation with other factors remain unclear. Integrative chromatin and transcriptional analysis following inhibition of RUNX1 and NOTCH1 revealed a surprisingly widespread role of RUNX1 in the establishment of global H3K27ac levels and that RUNX1 is required by NOTCH1 for cooperative transcription activation of key NOTCH1 target genes including MYC, DTX1, HES4, IL7R, and NOTCH3. Super-enhancers were preferentially sensitive to RUNX1 knockdown and RUNX1-dependent super-enhancers were disrupted following the treatment of a pan-BET inhibitor, I-BET151.
Project description:Runt-related transcription factor 1 (RUNX1) is oncogenic in diverse types of leukemia and epithelial cancers where its expression is associated with poor prognosis. Current models suggest that RUNX1 cooperates with other oncogenic factors (e.g., NOTCH1, TAL1) to drive the expression of proto-oncogenes in T cell acute lymphoblastic leukemia (T-ALL) but the molecular mechanisms controlled by RUNX1 and its cooperation with other factors remain unclear. Integrative chromatin and transcriptional analysis following inhibition of RUNX1 and NOTCH1 revealed a surprisingly widespread role of RUNX1 in the establishment of global H3K27ac levels and that RUNX1 is required by NOTCH1 for cooperative transcription activation of key NOTCH1 target genes including MYC, DTX1, HES4, IL7R, and NOTCH3. Super-enhancers were preferentially sensitive to RUNX1 knockdown and RUNX1-dependent super-enhancers were disrupted following the treatment of a pan-BET inhibitor, I-BET151.
Project description:Chromatin accessibility of T-cell acute lymphoblastic leukemia (T-ALL) cells with depletion or inhbiiton of cBAF complex [ATAC-seq]
Project description:Pkm1 and Pkm2 kinases are expressed in differentiating skeletal myoblasts. Knockdown of Pkm1 or Pkm2, therefore, can affect myoblast differentiation, by two independent regulatory mechanisms involving histone phosphorylation and chromatin remodeling complexes. Pkm2 KD in C2C12 cells reduced the chromatin marks of phosphorylated H3-T6, H3-T11 and H3-T45 into several essential myogenic promoters, and consequently, prevented their expression. Also, the transcriptional analysis demonstrated that Pkm2 is required for the expression of the cBAF-specific subunits Dpf2 and Baf250a, which we have previously demonstrated are essential for myogenesis. In contrast, Pkm1 KD alters the localization of nuclear Dpf2 into the cytoplasm as well. Mechanistically, Pkm KD resulted in decreased binding of cBAF components to their myogenic target genes, which also suggested a positive regulation between the cBaf complex and the H3 phosphorylation marks.