MYT1 attenuates neuroblastoma cell differentiation by inhibiting retinoic acid signaling pathway
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128054 | GEO | 2019/12/01
REPOSITORIES: GEO
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Project description:MYT1 attenuates neuroblastoma cell differentiation by inhibiting retinoic acid signaling pathway
| PRJNA526212 | ENA
Project description:Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell-type and developing stage-specific activity is largely unknown. In this study, we aimed to isolate the histone demethylase LSD1 complex from neural cells by biochemical purification. In so doing, we identified MyT1 as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation. Neuro2a cells were treated with either siControl, siLSD1 or siMyT1 for 48 h (n=3)
2014-05-20 | E-GEOD-49685 | biostudies-arrayexpress
Project description:Neuroblastoma is a pediatric tumor that accounts for more than 15% of cancer-related deaths in children. Survival chances for high-risk patients are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumors respond to retinoic acid-mediated differentiation. Among neuroblastoma tumors, two phenotypically distinct cell types-adrenergic (ADRN) and mesenchymal (MES), have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries. We hypothesized that distinct super-enhancers in these different tumor cells could mediate differential response to retinoic acid. To this end, we treated four different neuroblastoma cell lines, comprising both ADRN (MYCN amplified and non-amplified) and MES subtypes, with retinoic acid and studied the super-enhancer landscape upon treatment and after removal of retinoic acid. Using H3K27ac ChIP-seq paired with RNA-seq, we compared the super-enhancers in cells that respond to retinoic acid-mediated differentiation versus those that fail to differentiate. We identified unique super-enhancers associated with cells differentiation; however, even among cells that respond to treatment, there was heterogeneity upon removal of retinoic acid, with MYCN amplified cells remaining differentiated whereas MYCN non-amplified cells reverted to a proliferative state. This study identifies regulatory super-enhancers as a plausible mechanism behind the differential response to retinoic acid-mediated differentiation.
2022-07-28 | GSE202239 | GEO
Project description:Neuroblastoma is a pediatric tumor that accounts for more than 15% of cancer-related deaths in children. Survival chances for high-risk patients are less than 50%. Retinoic acid treatment is part of the maintenance therapy given to neuroblastoma patients; however, not all tumors respond to retinoic acid-mediated differentiation. Among neuroblastoma tumors, two phenotypically distinct cell types-adrenergic (ADRN) and mesenchymal (MES), have been identified based on their super-enhancer landscape and transcriptional core regulatory circuitries. We hypothesized that distinct super-enhancers in these different tumor cells could mediate differential response to retinoic acid. To this end, we treated four different neuroblastoma cell lines, comprising both ADRN (MYCN amplified and non-amplified) and MES subtypes, with retinoic acid and studied the super-enhancer landscape upon treatment and after removal of retinoic acid. Using H3K27ac ChIP-seq paired with RNA-seq, we compared the super-enhancers in cells that respond to retinoic acid-mediated differentiation versus those that fail to differentiate. We identified unique super-enhancers associated with cells differentiation; however, even among cells that respond to treatment, there was heterogeneity upon removal of retinoic acid, with MYCN amplified cells remaining differentiated whereas MYCN non-amplified cells reverted to a proliferative state. This study identifies regulatory super-enhancers as a plausible mechanism behind the differential response to retinoic acid-mediated differentiation.
2022-07-28 | GSE201179 | GEO
Project description:Here we performed a ChIP-seq experiment on a sample of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible HA-tagged version of the proneural factor MyT1 (MyT1-HA, under TetON control) after activation by doxycycline hyclate (DOX). This resulted in the generation of a genome-wide map of MyT1-HA binding to chromatin.
2016-09-09 | E-MTAB-4330 | biostudies-arrayexpress
Project description:Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell-type and developing stage-specific activity is largely unknown. In this study, we aimed to isolate the histone demethylase LSD1 complex from neural cells by biochemical purification. In so doing, we identified MyT1 as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation.
2014-05-20 | GSE49685 | GEO
Project description:To investigate a role of mKIAA genes in early stage of neurite outgrowth, in vitro time course experiment was performed using the mouse neuroblastoma Neuro2A cells and all-trans-retinoic acid. Six time points of 8 biological replicates were performed.These data were normalized by median intensities and subtracted background intensities. NOTE: Outlier involved several data were not deposited. Keywords: time-course
2005-04-28 | GSE2570 | GEO
Project description:Here we performed a microarray experiment on samples of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible version of the transcription factor MyT1 (MyT1-V5 TetON) under normal growth conditions and after 4 hours of treatment by doxycyline. This resulted in the generation of a genome-wide mRNA expression pattern and quantification for these cells in the two conditions.
2016-09-09 | E-MTAB-4335 | biostudies-arrayexpress
Project description:We report the changes in gene expression in U87 glioblastoma cells with re-introduced Myt1 or Myt1l.
2018-01-24 | GSE103790 | GEO
Project description:Members of the Myt (myelin transcription factor) family have been implicated in neuronal development. However, their in vivo roles in OL lineage development have not been systematically investigated. Here, we identified Myt1 transcription factor as a crucial regulator of oligodendrocyte differentiation in the developing central nervous system. Conventional knockout of Myt1 causes a remarkable delay in the initiation of OL differentiation, without affecting the generation and proliferation of OPCs. Conversely, hyperactivation of Myt1 induces precocious OL differentiation both in vitro and in vivo. Using a combination of RNA-seq and ChIP-seq analyses, we identified Nkx2.2 as a key target of Myt1 to switch on the OL differentiation program. Mechanistically, specific binding of Myt1 in the Nkx2.2 gene loci inhibits the nucleosomal histone deacetylation via hindering the HDAC1 repressor complex integrity and reducing the deacetylation activity of HDAC1. Additionally, we demonstrated that Myt1 functions downstream of Notch signaling pathway in controlling the timing of OL differentiation. Collectively, our data demonstrate that Myt1 is a major regulator of OL differentiation and provide insight into the epigenetic regulatory mechanisms under OL development. Myt1 is, therefore, a promising therapeutic target for enhancing the OL differentiation and myelination/remyelination during development or after demyelination insults.
2024-10-01 | GSE253491 | GEO