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LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [proliferation vs differentiation]

ABSTRACT: LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [proliferation vs differentiation]

PROVIDER: PRJNA552360 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9636790.fastq.gz	Fastqsanger.gz
	SRR9636800.fastq.gz	Fastqsanger.gz
	SRR9636791.fastq.gz	Fastqsanger.gz
	SRR9636801.fastq.gz	Fastqsanger.gz
	SRR9636792.fastq.gz	Fastqsanger.gz

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Similar Datasets

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors

Project description:LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors

| PRJNA552480 | ENA

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [inhibitors]

Project description:LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [inhibitors]

| PRJNA552362 | ENA

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [ChIP-seq]

Project description:LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [ChIP-seq]

| PRJNA551890 | ENA

LSD1 Inhibition Promotes Epithelial Differentiation through Derepression of Fate-Determining Transcription Factors.

Project description:Self-renewing somatic tissues depend upon the proper balance of chromatin-modifying enzymes to coordinate progenitor cell maintenance and differentiation, disruption of which can promote carcinogenesis. As a result, drugs targeting the epigenome hold significant therapeutic potential. The histone demethylase, LSD1 (KDM1A), is overexpressed in numerous cancers, including epithelial cancers; however, its role in the skin is virtually unknown. Here we show that LSD1 directly represses master epithelial transcription factors that promote differentiation. LSD1 inhibitors block both LSD1 binding to chromatin and its catalytic activity, driving significant increases in H3K4 methylation and gene transcription of these fate-determining transcription factors. This leads to both premature epidermal differentiation and the repression of squamous cell carcinoma. Together these data highlight both LSD1's role in maintaining the epidermal progenitor state and the potential of LSD1 inhibitors for the treatment of keratinocyte cancers, which collectively outnumber all other cancers combined.

| S-EPMC6719800 | biostudies-literature

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [inhibitors]

Project description:We report the impact of the pharmacological inhibition of the Histone 3 Lysine 4 demethylase (H3K4) LSD1 (KDM1A) enzymatic activity on genome-wide gene expression in normal human epidermal keratinocyte (NHEK)

2019-08-20 | GSE133737 | GEO

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [proliferation vs differentiation]

Project description:Genome-wide gene expression changes triggered by Ca2+-induced differentiation of epidermal progenitors

2019-08-20 | GSE133738 | GEO

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors [ChIP-seq]

Project description:We report the impact of the pharmacological inhibition of the Histone 3 Lysine 4 demethylase (H3K4) LSD1 (KDM1A) enzymatic activity on its binding genome wide and how it impacts genome-wide H3K4me1 and H3K4me2 deposition in Normal Human Epidermal Keratinocytes (NHEK)

2019-08-20 | GSE133560 | GEO

LSD1 inhibition promotes epithelial differentiation through derepression of fate- determining transcription factors

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

2019-08-20 | GSE133766 | GEO

LSD1 inhibition induces differentiation and cell death in Merkel cell carcinoma

Project description:Merkel cell carcinoma (MCC) is a highly aggressive, neuroendocrine skin cancer that lacks actionable mutations, which could be utilized for targeted therapies. Epigenetic regulators governing cell identity may represent unexplored therapeutic entry points. Here, we targeted epigenetic regulators in a pharmacological screen and discovered that the lysine-specific histone demethylase 1A (LSD1/KDM1A) is required for MCC growth in vitro and in vivo. We show that LSD1 inhibition in MCC disrupts the LSD1-CoREST complex leading to displacement and degradation of HMG20B (BRAF35), a poorly characterized complex member that is essential for MCC proliferation. Inhibition of LSD1 causes derepression of transcriptional master regulators of the neuronal lineage, activates a gene expression signature resembling normal Merkel cells, and induces cell cycle arrest and cell death. Our study unveils the importance of LSD1 for proliferation and maintaining cell identity in MCC. There is growing evidence that cancer cells exploit cellular plasticity and dedifferentiation programs to evade destruction by the immune system. The combination of LSD1 inhibitors with checkpoint inhibitors may thus represent a promising treatment strategy for MCC patients.

2020-11-03 | PXD020590 | Pride

Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for Retinoic Acid induced differentiation

Project description:The histone demethylase LSD1 is deregulated in several tumors, including leukemias, providing the rationale for the clinical use of LSD1 inhibitors. In acute promyelocytic leukemia (APL), pharmacological doses of retinoic acid (RA) induce differentiation of APL cells through degradation of the PML-RAR oncogene. APL cells are resistant to LSD1 inhibition or knock-out, but LSD1 inhibition sensitizes them to physiological doses of RA without altering the stability of PML-RAR, and extends survival of leukemic mice upon RA treatment. Non-enzymatic activities of LSD1 are essential to block differentiation of leukemic cells, while the combination of LSD1 inhibitors (or LSD1 knock-out) with low doses of RA releases a differentiation-associated gene expression program, not strictly dependent on changes in histone H3K4 methylation (known substrate of LSD1). An integrated proteomic/epigenomic/mutational analysis showed that LSD1 inhibitors alter the recruitment of LSD1-containing complexes to chromatin through inhibition of the interaction between LSD1 and GFI1, a relevant transcription factor in hematopoiesis.

2020-05-26 | PXD012954 | Pride

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