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E95a6f4f-3587-4332-a380-432c6c7c024a - samples

ABSTRACT: High-throughput chromosome conformation capture (Hi-C) data generated for cohesin-mutated (STAG2 or RAD21) and cohesin-wildtype AMLs.

PROVIDER: EGAD00001011198 | EGA |

REPOSITORIES: EGA

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487d40b4-bd7d-4fa7-8c6f-88acea5a1255 - samples

Project description:ChIP-seq targeting the H3K27ac histone modification in cohesin-mutated (STAG2 or RAD21 mutation) and cohesin wildtype (CTRL-AMLs) AMLs.

| EGAD00001011204 | EGA

5e6c15fb-fd9d-4a55-bbb3-bf031b8e9d4b - samples

Project description:ChIP-Seq targeting CTCF in cohesin-mutated (STAG2 or RAD21 mutations) and wildtype adult AMLs (CTRL-AMLs).

| EGAD00001011200 | EGA

6d76ec56-a250-4ac1-9da1-261be65fa15f - samples

Project description:ATAC-seq (Illumina TDE1 Transposase) to profile accessible chromatin regions of cohesin-mutated (STAG2 or RAD21 mutations) and -wildtype adult AMLs.

| EGAD00001011267 | EGA

04e9a0ab-7f31-4dc8-bfa8-9ee1f7d94bcf - samples

Project description:ChIPseq targeting the cohesin subunit STAG1 in STAG2-mutated AMLs or cohesin wildtype AMLs

| EGAD00001011206 | EGA

ea1b5928-f11a-4df1-9290-6aba4b1cf95e - samples

Project description:ChIP-Seq targeting the cohesin subunit STAG2 in STAG2-mutant or cohesin wildtype adult AMLs.

| EGAD00001011205 | EGA

7bd46198-2c95-478c-8e05-fdf4d6eabdc0 - samples

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.

| EGAD00001011207 | EGA

Cohesin Mutations in AML

Project description:Cohesin shapes the nuclear chromatin architecture, including enhancer-promoter interactions, and its components, of which especially STAG2 and RAD21, are frequently mutated in myeloid malignancies. To elucidate mechanisms of leukemogenesis associated with cohesin mutations in humans, we comprehensively characterized genetic, epigenetic, transcriptional, and chromatin conformational changes in acute myeloid leukemia (AML). To corroborate our findings, we performed complementary siRNA-mediated depletion of STAG2, its paralogue STAG1 or RAD21 in cord blood-derived CD34+ primary human hematopoietic stem and progenitor cells (HSPCs). We show that STAG2 mutations consistently lead to the loss of STAG2 protein and are associated with a specific set of co-occurring mutations, while STAG1 was never mutated in AML. Loss of STAG2 was frequently compensated by STAG1. Still, specific loci displayed altered cohesin occupancy, gene expression and corresponding changes in local chromatin activation as measured by H3K27ac enrichment and chromatin accessibility. High-throughput chromosome conformation capture (in-situ Hi-C) revealed significantly altered chromatin looping in cohesin-mutated AMLs, including weakened enhancer-promoter contacts with reduced, cohesin-dependent promoter activity. In HSPCs, we detected transcriptomic and epigenetic effects overlapping STAG2-mutant AML-specific changes following STAG2 knockdown (KD), that were not invoked by the depletion of STAG1. We also found that STAG2 loss in cultured HSPCs impaired the differentiation capacity, especially erythroid colony formation which maintained HSPC-like gene expression. This work establishes STAG2 as a key regulator of cohesin-associated chromatin architecture, gene expression and differentiation in the human hematopoietic system and identifies candidate target genes that may be implicated in leukemogenesis.

| EGAS00001007405 | EGA

e8d3e212-6d12-4da3-ae92-72980eb14a7b - samples

Project description:Transcriptomic data generated by RNA-sequencing for adult human AMLs with STAG2 or RAD21 mutations or no cohesin mutations (CTRL-AMLs).

| EGAD00001011197 | EGA

32a1b43f-aba4-4d4d-a192-aa35f32e6ebd - samples

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.

| EGAD00001011199 | EGA

Gene expression profiling from cohesin knockdown cells obtained grown in methylcellulose

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.

2015-09-16 | E-GEOD-72368 | biostudies-arrayexpress

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