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Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1

ABSTRACT: Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1

PROVIDER: PRJNA420508 | ENA |

REPOSITORIES: ENA

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Cistrome analysis of SKI and RUNX1 in HL60

Project description:SKI is a transcriptional co-regulator and overexpressed in various human tumors, for example in acute myeloid leukemia (AML). SKI contributes to the origin and maintenance of the leukemic phenotype. Here we use ChIP-seq and RNA-seq to identify the epigenetic alterations induced by SKI overexpression in AML cells. We show that approximately two thirds of differentially expressed genes are up-regulated upon SKI deletion, of which nearly 50% harbour SKI binding sites in their proximity, primarily in enhancer regions. Gene ontology analysis reveals that many of the differentially expressed genes are annotated to hematopoietic cell differentiation and inflammatory response, corroborating our finding that SKI deletion causes a release of the myeloid differentiation block in HL60 cells. We find that SKI peaks are enriched for RUNX1 consensus motifs, particularly in up-regulated SKI targets. RUNX1 ChIP-seq demonstrates that nearly 70% of RUNX1 binding sites overlap with SKI peaks, mainly at enhancer regions. SKI and RUNX1 co-occupy the same genomic sites and cooperate in gene silencing. Our work demonstrates for the first time on a genome-wide scale the predominant co-repressive function of SKI in AML cells and uncovers the transcription factor RUNX1 as an important mediator of SKI-dependent transcriptional repression.

2018-02-07 | GSE107553 | GEO

Cistrome analysis of SKI and RUNX1 in HL60

Project description:Cistrome analysis of SKI and RUNX1 in HL60

| PRJNA420513 | ENA

Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1.

Project description: Not available

| S-EPMC5909421 | biostudies-literature

Combined cistrome and transcriptome analysis of SKI in AML cells identifies SKI as a co-repressor for RUNX1

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-02-07 | GSE107556 | GEO

Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia

Project description:Despite absent expression in normal hematopoiesis, the Forkhead factor FOXC1, a critical mesenchymal differentiation regulator, is highly expressed in ~30% of HOXAhigh AML to confer blocked monocyte/macrophage differentiation. Through integrated proteomics and bioinformatics, we discovered that FOXC1 and RUNX1 interact through Forkhead and Runt domains respectively and cooccupy primed and active enhancers distributed close to differentiation genes. FOXC1 stabilises association of RUNX1, HDAC1 and Groucho repressor TLE3 to limit enhancer activity: FOXC1 knockdown induced loss of repressor proteins, gain of CEBPA binding, enhancer acetylation and upregulation of nearby genes, including KLF2. Furthermore, it triggered genome-wide redistribution of RUNX1, TLE3 and HDAC1 from enhancers to promoters leading to repression of self-renewal genes including MYC and MYB. Our studies highlight RUNX1 and CEBPA transcription factor swapping as a feature of leukemia cell differentiation, and reveal that FOXC1 prevents this by stabilising enhancer binding of a RUNX1/HDAC1/TLE3 transcription repressor complex, to oncogenic effect.

2021-08-08 | PXD027740 | Pride

SK-NEP-1 treated with SKI-5C

Project description:Wilm’s tumor(WT) is the most common malignant renal tumor in children, representing approximately 6-14% of all childhood cancers and about 95% of all pediatric renal malignancies. SKI-5C is a newly developed Sphk1 inhibitor. This small molecular inhibitor was firstly reported at 2009 by Wang et al. This study investigated the antitumor activity of SKI-5C in SK-NEP-1 cells. SKI-5C inhibited cell proliferation of SK-NEP-1 cells in a dose-dependent manner. Annexin V, Tunel and Hochest 33342 staining analysis showed that SKI-5C-treated cells showed more apoptotic features compared with the control.

2016-12-31 | GSE72980 | GEO

Transcriptome analysis of SKI knock-out in HL60 cells

Project description:Whole transcriptome for SKI knock-out and control HL60 cells was sequenced. SKI control and knockout samples were compared to find differentially expressed genes. Differentially expressed genes were further analysed to find the significance of SKI in HL60 cells.

2018-02-07 | GSE107555 | GEO

HDAC3 preferentially binds to RUNX1 in t(8;21) AML cells and collaborates with RUNX1 to repress AML1-ETO-mediated transcriptional activation

Project description:Human histone deacetylase 3 (HDAC3) plays an important role in gene transcription in diseased human cells, such as leukemia. The t(8;21) chromosomal translocation is one of the most commonly observed genetic abnormalities associated with acute myeloid leukemia. This translocation generates the AML1-ETO fusion protein between the wild-type RUNX1 transcription factor and wild-type ETO transcriptional corepressor. To better understand the role of HDAC3 in t(8;21) leukemogenesis, the human HDAC3-containing complexes were isolated from stably-transfected HeLa cells by using anti-FLAG immunoprecipitation. The resulting complexes were resolved in SDS-PAGE. The components of the complexes were identified using LC-MS/MS. We report here that the human RUNX1 transcription is a component of the HDAC3 complexes. We demonstrate that HDAC3 and RUNX1 collaboratively repress AML1-ETO-mediated transcription. These results reveal new insight into how AML1-ETO, RUNX1, and HDAC3 crosstalk to deregulate gene transcription in t(8;21) leukemia cells.

2020-02-17 | PXD017230 | Pride

Reversing SKI–SMAD4-mediated suppression is essential for TH17 cell differentiation

Project description:Disruption of Ski/Smad4 license Th17 differentiation. TGF-b-Ski-Smad4-RORgt-Th17 axis

2017-10-25 | GSE101527 | GEO

Identification of CEBPA and RUNX1 interactors in 3q-rearranged AML

Project description:Chromatin immunoprecipitation with specific isolation of chromatin associated proteins (ChIP-SICAP) was used to identify chromatin-bound interactors of CEBPA and RUNX1 in the 3q-rearranged human myeloid leukemia cell line MUTZ-3.

2021-04-29 | PXD020045 | Pride

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