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ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 2]

ABSTRACT: Notch signaling is the most prevalent oncogenic pathway in T-ALL, but clinical trials showed that pan-Notch inhibitors caused dose-limiting toxicities. Thus, we shifted our focus from Notch to ETS1, which is one of the top transcription factors that most frequently co-bind Notch-occupied regulatory elements in the T-ALL context. A top essential ETS1-dependent element was a Notch-bound enhancer at +140kb from MYB that we named the ETS-MYB enhancer (E-Me). Using genetically engineered mouse models and chromatin profiling, we showed that the E-Me selectively promotes self-renewal of hematopoietic stem cells, becomes inactive in committed T cell progenitors; and is reactivated to promote Notch-induced transformation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263913 | GEO | 2025/09/25

REPOSITORIES: GEO

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ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 1]

Project description:Notch signaling is the most prevalent oncogenic pathway in T-ALL, but clinical trials showed that pan-Notch inhibitors caused dose-limiting toxicities. Thus, we shifted our focus from Notch to ETS1, which is one of the top transcription factors that most frequently co-bind Notch-occupied regulatory elements in the T-ALL context. A top essential ETS1-dependent element was a Notch-bound enhancer at +140kb from MYB that we named the ETS-MYB enhancer (E-Me). Using genetically engineered mouse models and chromatin profiling, we showed that the E-Me selectively promotes self-renewal of hematopoietic stem cells, becomes inactive in committed T cell progenitors; and is reactivated to promote Notch-induced transformation.

2025-09-25 | GSE263585 | GEO

ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia.

Project description:ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia.

| PRJNA1100450 | ENA

ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 2]

Project description:ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 2]

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ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 1]

Project description:ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 1]

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ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia.

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

2025-09-25 | GSE263952 | GEO

Ets1 confers context-dependent activation of Notch signaling in T-cell leukemia [RNA-Seq]

Project description:Notch activation is highly prevalent in several cancers, including more than 60% of cases of T-cell acute lymphoblastic leukemia (T-ALL). However, the use of pan-Notch inhibitors to treat cancers has been hampered by excessive toxicities, particularly affecting intestinal health. In order to combat Notch-driven oncogenic signals with less toxicity, one strategy is to target the transcriptional cofactors that promote tissue-specific Notch activation. We previously showed that Zmiz1 is a direct Notch1 cofactor that selectively promotes T-cell development and leukemogenic functions of Notch1. Ets1 is an excellent candidate as a transcription factor (TF) that promotes Notch functions selectively in T-ALL since the scope of Ets1 expression is far more limited than Notch expression and since Ets1 co-occupies Notch-bound enhancers with high frequency. Here, we used comparative ChIP-Seq and gene expression methods to show that Ets1 withdrawal impaired Notch complex recruitment and H3K27 acetylation at co-bound enhancers and disabled shared oncogenic pathways. ChIP-Seq showed that Ets1 peaks overlapped with 73-76% of Zmiz1 peaks and 71-75% of Notch1 peaks. Ets1 knockdown reduced Notch1, Rbpj, and Zmiz1 occupancy at enhancers that regulate genes that drive T-cell differentiation and/or T-ALL proliferation. RNA-Seq showed that Ets1 coregulated ~22% of Notch target genes with induction of Myc as a dominant and functional contribution. Our data support an emerging model in which transcription factors like Ets1 assist Notch in activating a subset of enhancers with important functions for T-cell leukemogenesis and development. Strategies that exploit the context dependence of Notch might combat the Notch pathway in cancer cells with less toxicity than pan-Notch inhibitors.

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Ets1 confers context-dependent activation of Notch signaling in T-cell leukemia [ChIP-Seq]

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Bidirectional enhancer RNAs regulate different MYB promoters

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2024-08-01 | GSE263511 | GEO

MYB-regulated pancreatic cancer secretome

Project description:Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks and altered biological pathways. We further investigated the secreted proteins for their potential biomarker properties.

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