Next-generation sequencing reveals a novel role of lysine-specific demethylase 1 in adhesion of rhabdomyosarcoma cells [ChIP-seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140039 | GEO | 2019/11/07
REPOSITORIES: GEO
Similar Datasets
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
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: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:Frozen skeletal muscle, tumor adjacent skeletal muscle, Endothelial Rhabdomyosarcoma (ERMS) and Alveolar Rhabdomyosarcoma (ARMS) samples were profiled on Illumina bead array. Total RNA from primary resected samples were profiled to allow comparison of 1) normal skeletal muscle tissue with RMS samples and 2) ARMS with ERMS tumors.
2013-12-31 | E-GEOD-28511 | biostudies-arrayexpress
Project description:Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-year survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-year survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in 3 cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was dramatically reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a striking reduction in tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data show that HNRNPH1 may be an important molecular target for the development of future RMS therapy.
2018-02-02 | GSE104559 | GEO
Project description:Genetic and shRNA-mediated inhibition of SIX1 expression in RMS cells induces myogenic differentiation and impedes RMS tumor growth. To elucidate the mechanism by which SIX1 loss activates a differentiation program, we performed SIX1, MYOD1, and H3K27ac ChIPseq in two SIX1 knockdown SMS-CTR cell lines and one control SMS-CTR cell line to profile changes in transcriptional activity and myogenic transcription factor binding in fusion-negative Rhabdomyosarcoma.
2022-02-07 | GSE173151 | GEO
Project description:Rhabdomyosarcoma (RMS) is a frequent non-epithelial tumor of soft tissue that originates from a myogenic differentiation defect. Expression of SNAIL transcription factor is elevated in the alveolar subtype of RMS, characterized by a low myogenic differentiation status and high aggressiveness. SNAIL affects RMS metastasis by reorganization of actin cytoskeleton, regulation of ezrin expression and chemotaxis to HGF and SDF-1. The differentiation of human RMS diminishes SNAIL level. SNAIL silencing completely abolishes the growth of human RMS xenotransplants. SNAIL inhibits myogenic differentiation of RMS by binding to the MYF5 promoter, suppressing its expression, displacing MYOD from canonical to alternative E-box sequences and regulating myomiRs expression. SNAIL silencing allows the re-expression of MYF5 and canonical MYOD binding, promoting RMS cell myogenic differentiation. These novel results open potential avenues for the development of innovative therapeutic strategies based on SNAIL silencing.
2020-07-14 | PXD006711 | Pride
Project description:Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma and resembles developing skeletal muscle. Specific genomic alterations including translocations, deletions and amplification events have been associated with the alveolar and embryonal subtypes of RMS. Characterizing these changes has led to increased understanding of the underlying molecular biology. However, further aberrations and their significance remain to be defined. Genomic copy number variations have been shown to affect the level of transcription in several tumor types. In this study, we have combined array comparative genomic hybridization analysis of 13 RMS cell lines, supported by confirmatory PCR analyses, with their corresponding expression profiles. This identified sets of genes that are altered in their level of expression by genomic imbalances. We also show that the effect on gene expression was proportional to the level of genomic gain or loss. Keywords: Rhabdomyosarcoma cell lines will be added later on
2009-06-04 | E-GEOD-8840 | biostudies-arrayexpress
Project description:Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with no precision therapy available for affected patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in representative cell lines and patient-derived xenografts to understand chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative rhabdomyosarcoma (FN-RMS). We have generated spike-in in situ Hi-C chromatin interaction maps for the commonest FP-RMS and FN-RMS cell lines, and compared our data with patient derived xenograft (PDX) models. In our studies we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains, and unique patterns of structural variation. This study enables a comprehensive resource for contextualizing gene regulation events in RMS, and high-depth chromatin interactivity maps for identification of functionally critical chromatin domains in this tumor.
2023-06-13 | GSE215172 | GEO
Project description:Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. Determine the role of LSD1 in androgen signaling.
2014-12-12 | E-GEOD-52201 | biostudies-arrayexpress