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Chromatin profiling upon pharmacological LSD1 inhibition in MCC [CUT&RUN]

ABSTRACT: Chromatin profiling upon pharmacological LSD1 inhibition in MCC [CUT&RUN]

PROVIDER: PRJNA623225 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11484783_1.fastq.gz	Fastqsanger.gz
	SRR11484783_2.fastq.gz	Fastqsanger.gz
	SRR11484784_1.fastq.gz	Fastqsanger.gz
	SRR11484784_2.fastq.gz	Fastqsanger.gz
	SRR11484785_1.fastq.gz	Fastqsanger.gz

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Chromatin profiling upon pharmacological LSD1 inhibition in MCC [CUT&RUN]

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.

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Pharmacological LSD1 inhibition in MCC

Project description:Pharmacological LSD1 inhibition in MCC

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Transcriptomic maps of pharmacological LSD1 inhibition in MCC [SLAMseq]

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Transcriptomic maps of pharmacological LSD1 inhibition in MCC [QUANTseq]

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Genome-wide chromatin accessibility mapping upon pharmacological LSD1 inhibition in MCC [ATACseq]

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Transcriptomic maps of pharmacological LSD1 inhibition in MCC [QUANTseq]

Project description:Transcriptomic maps of pharmacological LSD1 inhibition in MCC [QUANTseq]

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Transcriptomic maps of pharmacological LSD1 inhibition in MCC [SLAMseq]

Project description:Transcriptomic maps of pharmacological LSD1 inhibition in MCC [SLAMseq]

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CUT & RUN analysis of H3K4me2 mark upon LSD1 inhibition

Project description:Lysine-specific demethylase 1 (LSD1) is a histone demethylase that promotes stemness and cancer cell survival, including in prostate cancer. LSD1 has been shown to perfrom catalytic independent function sto promote prostate cancer survival. Here, we tested the levels of LSD1's canonical target H3K4me2 upon LSD1 inhibition with SP2509 across the genome using CUT and RUN analysis.

2023-08-30 | GSE235211 | GEO

LSD1 transcriptome analysis in Merkel cell carcinoma (MCC) cell lines

Project description:Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin, caused by either excessive UV damage or integration of the Merkel cell polyomavirus (MCV) genome. Here, we report that virally encoded MCV small T antigen (ST) establishes dependence on the LSD1 transcriptional repressor. Inhibition of LSD1 reduces growth of MCV-positive MCC and suppresses ST’s transformation capacity in vitro and in vivo. To define the mechanism of LSD1 inhibition in MCC, we performed a CRISPR loss-of-function library screen. We found that deletion of components of the non-canonical (ncBAF) chromatin remodeler complex confers resistance to LSD1 inhibitors and that LSD1 and ncBAF antagonistically regulate an overlapping set of genes involved in neuron differentiation. Our work provides mechanistic insight into the dependence of MCC on LSD1 and the role of ncBAF as a tumor suppressor in cancer.

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Genome-wide chromatin accessibility mapping upon pharmacological LSD1 inhibition in MCC [ATACseq]

Project description:Genome-wide chromatin accessibility mapping upon pharmacological LSD1 inhibition in MCC [ATACseq]

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