Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ChIP-seq for histone acetylation and methylation in THP-1 cells treated with LSD1 inhibitor INCB059872

ABSTRACT: INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We performed ChIP-seq for histone modifications to define the earliest regulatory events associated with INCB059872 treatment. Changes in acetylation were more dramatic than changes in methylation, and these changes could be traced back to a loss of CoREST activity at GFI1-regulated targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145166 | GEO | 2020/05/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PRO-seq of THP-1 cells treated with LSD1 inhibitor INCB059872

Project description:INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We used precision nuclear run-on sequencing (PRO-seq) to define early transcriptional changes associated with INCB059872 treatment. Changes in nascent transcription could be traced back to a loss of CoREST activity resulting in activation of GFI1-regulated targets.

2020-05-28 | GSE145071 | GEO

RNA-seq of MV-4-11 or THP-1 cells treated with LSD1 inhibitor INCB059872

Project description:INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. LSD1 inhibition can induce differentiation of acute myeloid leukemia (AML), and here we have used RNA-seq to measure the transcriptional changes caused by INCB059872 in two AML cell lines.

2020-05-28 | GSE145106 | GEO

RNA-seq of murine megakaryocyte progenitor cells treated with LSD1 inhibitor INCB059872

Project description:INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We identified a population of cells within murine lineage-negative bone marrow that is expanded after treatment with INCB059872. Here we sorted cells from this population (Lin- Cd41+ Cd200r3-) and performed RNA-seq to measure gene expression changes caused by INCB059872. Consistent with the thrombocytopenia observed in LSD1i-treated mice, INCB059872 reduced expression of genes associated with platelet function.

2020-05-28 | GSE145211 | GEO

Single-cell RNA-seq of AML patient bone marrow treated with INCB059872, azacitidine, or combination

Project description:INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. We evaluated a pre-treatment bone marrow sample of a patient who showed a clinical response to INCB059872 + azacitidine treatment. Single-cell RNA-sequencing (scRNA-seq) showed that INCB059872 caused a shift in gene expression that was associated with GFI1/GFI1B regulation.

2020-05-28 | GSE145410 | GEO

Single-cell RNA-seq: INCB059872 in wild-type murine bone marrow

Project description:INCB059872 is a selective irreversible inhibitor of Lysine-Specific Demethylase 1 (LSD1) that is in phase 1 clinical trials in hematopoietic malignancies. Mice treated with INCB059872 had reduced platelet counts within 4 days of treatment. Here, we used single-cell RNA-seq to study the effects of INCB059872 on hematopoietic progenitor populations within wild-type murine bone marrow. Our results showed that INCB059872 triggered accumulation of megakaryocyte early progenitor cells with gene expression hallmarks of stem cells, which may begin to explain the thrombocytopenia observed in patients treated with LSD1 inhibitors.

2020-05-28 | GSE145279 | GEO

Targeted inhibition of GFI1/KDM1A combined with BET inhibitor augments lethal activity against AML including post-MPN sAML cells [RNA-seq]

Project description:To determine the impact of inhibition of KDM1A/LSD1 through genetic manipulation by CRISPR/Cas9 or inducible shRNA or following treatment with irreversible LSD1 inhibitor INCB059872 on global transcriptomic profile in AML and post-MPN sAML cells. To determine the impact of GFI1 knockdown on global transcriptomic profile in AML cells.

2021-05-26 | GSE160303 | GEO

PRO-seq of THP-1 cells treated with LSD1 inhibitor INCB059872

Project description:PRO-seq of THP-1 cells treated with LSD1 inhibitor INCB059872

| PRJNA605859 | ENA

HMG20B stabilizes interaction of LSD1 with GFI1 on chromatin to confer 1 transcription repression and leukemia cell differentiation block

Project description:Pharmacologic inhibition of LSD1 induces molecular and morphologic differentiation of blast cells in acute myeloid leukaemia (AML) patients harboring MLL gene translocations. In addition to its demethylase activity, LSD1 has a critical scaffolding function at genomic sites occupied by the SNAG domain transcription repressor GFI1. Importantly, inhibitors block both enzymatic and scaffolding activities, in the latter case by disrupting the protein:protein interaction of GFI1 with LSD1. To explore the wider consequences of LSD1 inhibition on the LSD1 protein complex we made use of mass spectrometry approaches. We discovered that the interaction of the HMG-box protein HMG20B with LSD1 was also disrupted by LSD1 inhibition. Downstream investigations revealed that HMG20B is colocated on chromatin genome-wide with GFI1 and LSD1; the strongest HMG20B binding colocates with the strongest GFI1 and LSD1 binding. Functional assays demonstrated that HMG20B depletion induces leukaemia cell differentiation and further revealed that HMG20B is required for the transcription repressor activity of GFI1 through stabilizing the interaction on chromatin of LSD1 with GFI1. Interaction of HMG20B with LSD1 is through its coiled-coil domain. Thus, HMG20B is a critical component of the GFI1:LSD1 transcription repressor complex which contributes to leukaemia cell differentiation block.

2023-03-11 | PXD030581 | Pride

SFMBT1 Functions with LSD1 to Regulate Expression of Canonical Histone Genes and Chromatin-Related Factors [RNA-Seq]

Project description:SFMBT1 is a poorly characterized mammalian MBT domain-containing protein homologous to Drosophila SFMBT, a Polycomb group protein involved in epigenetic regulation of gene expression. Here, we show that SFMBT1 regulates transcription in somatic cells and during spermatogenesis through the formation of a stable complex with LSD1 and CoREST. When bound to its gene targets, SFMBT1 recruits its associated proteins and causes chromatin compaction and transcriptional repression. SFMBT1, LSD1, and CoREST share a large fraction of target genes including those encoding replication-dependent histones. Simultaneous occupancy of histone genes by SFMBT1, LSD1, and CoREST is regulated during the cell cycle and correlates with the loss of RNA polymerase II at these promoters during G2, M, and G1. The interplay between the repressive SFMBT1M-bM-^@M-^SLSD1M-bM-^@M-^SCoREST complex and RNA polymerase II contributes to the timely transcriptional regulation of histone genes in human cells. SFMBT1, LSD1, and CoREST also form a stable complex in germ cells and their chromatin binding activity is regulated during spermatogenesis. RNA-seq in HeLaS3 cells ctrl compared to triple knockdown for SFMBT1, CoREST, and LSD1

2013-03-26 | E-GEOD-45442 | biostudies-arrayexpress

RNA-seq of MV-4-11 or THP-1 cells treated with LSD1 inhibitor INCB059872

Project description:RNA-seq of MV-4-11 or THP-1 cells treated with LSD1 inhibitor INCB059872

| PRJNA606049 | ENA