Similar Datasets
Project description:Inhibition of lysine-specific demethylase 1 inhibition in glioblastoma
| PRJNA929532 | ENA
Project description:Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.
2024-11-10 | GSE261471 | GEO
Project description:Lysine-specific demethylase 1 (LSD1/KDM1A) is a pivotal epigenetic enzyme that contributes to several malignancies including malignant glioma. LSD1 is a flavin adenine dinucleotide dependent histone demethylase that specifically targets histone H3 lysine (K) 4 mono- (me1) and di-methylation (me2) and H3K9me1/2 for demethylation. Herein we report the development of an LSD inhibitor, S2172, which efficiently penetrates the blood-brain barrier. S2172 effectively suppresses LSD1 enzymatic activity, resulting in the depletion of cell growth both in vitro in glioma stem cells (GSCs) (mean half-maximal inhibitory concentration (IC50) of 13.8 μM) and in vivo in a GSC orthotopic xenograft mouse model. Treatment with S2172 robustly reduced the expression of the stemness-related genes MYC and Nestin in GSC cells. Consistent with this, chromatin immunoprecipitation-sequencing revealed a significant S2172-dependent alteration in H3K4me2/H3K4me3 status. Furthermore, we identified 284 newly acquired H3K4me2 peak regions after S2172 treatment, which were encompassed within super-enhancer regions. The altered H3K4me2/H3K4me3 status induced by S2172 treatment affected the expression of genes related to tumorigenesis. Our data suggest that targeting LSD1 with S2172 could provide a promising treatment option for glioblastomas, particularly due to targeting of GSC populations.
2024-11-10 | GSE261472 | GEO
Project description:We report the identification of LSD1 binding genomic regions in mouse embryonic stem cells (ESC) by high throughput sequencing. By obtaining over 10 million 36 bp reads of sequence from each chromatin immunoprecipitated DNA, we generated genome-wide maps for LSD1 and histone H3 dimethylated on lysine 4 (H3K4me2), the substrate for LSD1 in mouse ESCs. Our results showed an extensive overlap between the LSD1 and H3K4me2 genomic regions and a correlation between the genomic levels of LSD1/H3K4me2 and gene expression, including many highly expressed ESC genes. LSD1 is recruited to the chromatin of cells in the G1/S/G2 phases and is displaced from the chromatin of M phase cells, suggesting that LSD1 or H3K4me2 alternatively occupies LSD1 genomic regions during cell cycle progression. LSD1 knockdown by RNA interference or its displacement from the chromatin by anti-neoplastic agents caused an increase in the levels of a subset of LSD1 target genes. Taken together, these results suggest that cell-cycle dependent association and dissociation of LSD1 with chromatin mediates short-time scale gene expression changes during ES cell cycle progression. Examination of LSD1 and lysine 4 dimethylated histone H3 (H3K4me2) binding genomic regions in embryonic stem cells. Input genomic DNA and DNA immunoprecipitaed with control IgG was included as controls.
2012-10-03 | E-GEOD-18515 | biostudies-arrayexpress
Project description:The aim of this study is to identify the LSD1 genome binding profile in adipocytes. LSD1 binding profile in fat cells - samples and experiments will continue to be added to this study over the course of the project.
2014-06-10 | E-GEOD-50934 | biostudies-arrayexpress
Project description:Lysine-specific demethylase 1 (LSD1) is involved in gene regulation and development; however, its precise function, molecular targets and underlying mechanisms during development are poorly understood. Here, we show that LSD1 is required for neuronal progenitor cell (NPC) maintenance during cortical development. A ChIP-seq analysis identified a LSD1 binding site (LBAL) downstream of Atrophin1 (ATN1). Surprisingly, tranylcypromine (LSD1 inhibitor) treatment increased H3K4 methylation at LBAL, leading to ATN1 repression and NPC differentiation. Knockdown of LSD1 and ATN1 phenocopied each other in inducing NPC premature differentiation and depletion which could be rescued by ATN1 overexpression, suggesting that LSD1 controls NPC differentiation via regulation of ATN1 methylation status and expression. The involvement of LSD1 in ATN1 expression and NPC maintenance were confirmed in knockout mice. These findings hint at the potential application for the clinical drug, tranylcypromine, in the prevention and/or treatment of ATN1-associated degenerative disease, dentatorubral-pallidoluysian atrophy. Examination of LSD1 binding sites in neuronal progenitor cells.
2015-04-29 | E-GEOD-62770 | biostudies-arrayexpress
Project description:The aim of this study is to identify the LSD1 target genes in metastatic androgen independent prostate cancer Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.
2017-04-25 | GSE57078 | GEO
Project description:The aim of this study is to identify the LSD1 target genes in metastatic androgen independent prostate cancer Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.
2017-04-25 | GSE57077 | GEO
Project description:We report the identification of LSD1 binding genomic regions in mouse embryonic stem cells (ESC) by high throughput sequencing. By obtaining over 10 million 36 bp reads of sequence from each chromatin immunoprecipitated DNA, we generated genome-wide maps for LSD1 and histone H3 dimethylated on lysine 4 (H3K4me2), the substrate for LSD1 in mouse ESCs. Our results showed an extensive overlap between the LSD1 and H3K4me2 genomic regions and a correlation between the genomic levels of LSD1/H3K4me2 and gene expression, including many highly expressed ESC genes. LSD1 is recruited to the chromatin of cells in the G1/S/G2 phases and is displaced from the chromatin of M phase cells, suggesting that LSD1 or H3K4me2 alternatively occupies LSD1 genomic regions during cell cycle progression. LSD1 knockdown by RNA interference or its displacement from the chromatin by anti-neoplastic agents caused an increase in the levels of a subset of LSD1 target genes. Taken together, these results suggest that cell-cycle dependent association and dissociation of LSD1 with chromatin mediates short-time scale gene expression changes during ES cell cycle progression.
2012-10-03 | GSE18515 | GEO
Project description:Lysine-specific demethylase 1 (LSD1) has been shown to be overexpressed in rhabdomyosarcoma (RMS) tumor samples. This study aims at elucidating changes in the RNA expression profile by RNA Sequencing in control and LSD1 knockdown conditions using transient silencing with siRNA. In addition, ChIP Sequencing was employed to investigate changes in the histone methylation pattern of H3K4me2 as a target of LSD1 in control and LSD1 knockdown conditions.
2019-11-07 | GSE140040 | GEO