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The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

ABSTRACT: The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

PROVIDER: PRJNA824444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18674211.fastq.gz	Fastqsanger.gz
	SRR18674212.fastq.gz	Fastqsanger.gz
	SRR18674213.fastq.gz	Fastqsanger.gz
	SRR18674214.fastq.gz	Fastqsanger.gz
	SRR18674215.fastq.gz	Fastqsanger.gz

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The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

Project description:The ETS transcription factor ERG is involved in several cancers including leukemia. However, ERG domains and co-factors involved in leukemogenesis remain largely uncharacterized and as a transcription factor it is currently undruggable. Here, we report a critical role for the conserved amino-acid proline at position 199, at the 3’ end of the PNT domain, for ERG’s leukemogenic activity. Specifically, we demonstrate that it is required for ERG-induced self-renewal and restriction of myeloid differentiation in hematopoietic progenitor cells and for initiation of leukemia in mouse transduction/transplantation models. Mechanistically, we show that P199 facilitates the interaction of ERG with the NCoR-HDAC3 co-repressor complex. Inhibition of HDAC3 reduced in vitro and in vivo growth of human ERG-dependent leukemic cells as well as growth of ERG dependent prostate cancer cells. Thus, the interaction of ERG with the NCoR-HDAC3 co-repressor complex is required for its oncogenic activity and modulation of this interaction may provide an opportunity for therapeutic intervention.

2023-05-26 | GSE200392 | GEO

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

2023-05-26 | GSE200391 | GEO

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

2023-05-26 | GSE200389 | GEO

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

Project description:The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

| PRJNA824443 | ENA

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

Project description:The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of ERG.

| PRJNA824425 | ENA

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG.

Project description:The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG's interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention.

| S-EPMC10514085 | biostudies-literature

A single amino acid at the PNT domain of ERG mediates its leukemogenic activity through interaction with the NCoR-HDAC3 co-repressor complex.

Project description:A single amino acid at the PNT domain of ERG mediates its leukemogenic activity through interaction with the NCoR-HDAC3 co-repressor complex.

| PRJNA824433 | ENA

Nuclear receptor corepressor (NCOR) and HDAC3 in hypothalamus [ChIP-Seq]

Project description:We determined genomic binding of HDAC3 in mouse hypothalamus by ChIP-seq, and identified target genes of the NCOR/HDAC3 complex in hypothalamus of NS-DADm (mutated deacetylase activation domain in NCORs) mice by RNA-seq.

2018-10-29 | GSE92451 | GEO

Nuclear receptor corepressor (NCOR) and HDAC3 in hypothalamus [RNA-Seq]

2018-10-29 | GSE92450 | GEO

HDAC3 ensures stepwise epidermal stratification via NCoR/SMRT-reliant mechanisms independent of its histone deacetylase activity (HDAC3 NCoRSMRT microarray)

Project description:Chromatin modifiers play critical roles in epidermal development, but the functions of histone deacetylases in this context are poorly understood. We find that the Class I HDAC, HDAC3, is expressed broadly in embryonic epidermis, and is required for its orderly stepwise stratification. Stability of HDAC3 protein in vivo is reliant on NCoR and SMRT, which function redundantly in epidermal development. However, point mutations in the NCoR and SMRT Deacetylase Activating Domains, which are required for HDAC3’s enzymatic function, permit normal stratification, indicating that HDAC3’s roles in this context are independent of its histone deacetylase activity. HDAC3 functions both in conjunction with, and independent of, KLF4 to repress premature expression of different sets of terminal differentiation genes and suppresses expression of inflammatory cytokines through a RelA-dependent mechanism. These data identify HDAC3 as a hub coordinating multiple aspects of epidermal barrier acquisition. We used microarrays to determine transcriptional changes in Hdac3 deleted epidermis compared to control and Ncor1/Ncor2 deleted epidermis compared to control.

2020-08-23 | GSE137234 | GEO

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