Project description:ChIP-seq targeting the H3K27ac histone modification in cohesin-mutated (STAG2 or RAD21 mutation) and cohesin wildtype (CTRL-AMLs) AMLs.
Project description:ATAC-seq (Illumina TDE1 Transposase) to profile accessible chromatin regions of cohesin-mutated (STAG2 or RAD21 mutations) and -wildtype adult AMLs.
Project description:High-throughput chromosome conformation capture (Hi-C) data generated for cohesin-mutated (STAG2 or RAD21) and cohesin-wildtype AMLs.
Project description:Transcriptomic data generated by RNA-sequencing for adult human AMLs with STAG2 or RAD21 mutations or no cohesin mutations (CTRL-AMLs).
Project description:Low-pass whole-genome DNA sequencing of cohesin-mutated (STAG2 or RAD21 mutations) and wildtype (CTRL-AML) adult AMLs generated generated from ultrasound-fragmented genomic DNA. Samples were only sequenced shallow (20-40 Mio reads) Used for digital karyotyping and ChIP-seq background/copy-nuber normalization/correction.
Project description:ChIP-Seq targeting the major cohesin core subunit RAD21 to represent cohesin occupancy and binding sites in cohesin-mutated (STA2 or RAD21 mutations) and wildtpye adult AMLs.
Project description:We performed RNA-sequencing in c-Kit+ cells that were infected with retroviruses expressing shRNAs for Renilla, Rad21, Smc1a, Smc3 or Stag2. These cells were grown in methylcellulose (M3434) for either one passage (P1) or replated for five passages (P5). RNA-sequencing control (Ren) and cohesin (Rad21, Smc1a, Smc3 and Stag2) knockdown cells.
Project description:Cohesin shapes the chromatin architecture, including enhancer-promoter interactions. Its components, especially STAG2 but not its paralogue STAG1, are frequently mutated in myeloid malignancies. To elucidate the underlying mechanisms of leukemogenesis, we comprehensively characterized genetic, epigenetic, transcriptional, and chromatin conformational changes in acute myeloid leukemia (AML) patient samples. Specific loci displayed altered cohesin occupancy, gene expression and local chromatin activation which were not compensated by STAG1. These changes could be linked to disrupted spatial chromatin looping in cohesin-mutated AMLs. We performed complementary depletion of STAG2 or STAG1 in primary human hematopoietic progenitors (HSPCs). We detected effects overlapping STAG2-mutant AML-specific changes following STAG2 knockdown, not invoked by depletion of STAG1. STAG2-deficient HSPCs displayed impaired differentiation capacity and maintained HSPC-like gene expression. This work establishes STAG2 as a key regulator of chromatin contacts, gene expression and differentiation in the hematopoietic system and identifies candidate target genes that may be implicated in human leukemogenesis.