Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA398019 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5928303_1.fastq.gz | Fastqsanger.gz | |||
| SRR5928303_2.fastq.gz | Fastqsanger.gz | |||
| SRR5928304_1.fastq.gz | Fastqsanger.gz | |||
| SRR5928304_2.fastq.gz | Fastqsanger.gz | |||
| SRR5928305_1.fastq.gz | Fastqsanger.gz |
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Project description:NR2F2 melanoma cellular models
| PRJNA398018 | ENA
Project description:Melanoma is a highly metastatic tumor type responsible of the large majority of the skin cancer-related deaths. Melanoma cells recapitulate the migratory and invasive nature of neural crest stem cells from which melanocytes arise. However, the mechanisms by which these developmental programs confer melanoma cells with more aggressive properties are not understood. Here we provide evidence for an epigenetically regulated developmental program that is aberrantly re-activated by melanoma cells to aid in the metastatic process. We reasoned that studying molecular changes occurring during the ontogeny of melanocytes from progenitor neural crest cells (NCC), and identifying developmental programs retained or re-gained by melanoma cells, could reveal crucial processes that modulate melanoma aggressiveness. Here we describe a novel mechanism that controls the activity of a transcriptional regulator of human neural crest, the Nuclear Receptor Subfamily 2 Group F, Member 2 (NR2F2). We find that highly localized DNA methylation acts as an on/off switch that controls the expression of a truncated NR2F2 isoform (NR2F2-Iso2) from an alternative transcription start site during NCC to melanocyte differentiation. We show that melanoma cells co-opt this developmental program by decreased DNA methylation and re-expression of NR2F2-Iso2 to promote melanoma metastasis. NR2F2-Iso2 regulates the transcriptional activity of the full length NR2F2 isoform 1 by impairing its binding to chromatin, which results in altered expression of NCC and differentiation genes. Our data demonstrate that epigenetic reactivation of NR2F2 isoform 2 promotes melanoma metastasis, which could be targeted for therapeutic purposes.
2023-02-12 | GSE102552 | GEO
Project description:Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-to mesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA-methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 – isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-binding domain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanoma progression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC associated target genes. Our findings indicate that DNA-methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.
2022-12-31 | GSE102542 | GEO
Project description:Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-to mesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA-methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 – isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-binding domain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanoma progression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC associated target genes. Our findings indicate that DNA-methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.
2022-12-31 | GSE213390 | GEO
Project description:Metastatic melanoma develops once transformed melanocytic cells begin to de-differentiate into migratory and invasive melanoma cells with neural crest cell (NCC)-like and epithelial-to mesenchymal transition (EMT)-like features. However, it is still unclear how transformed melanocytes assume a metastatic melanoma cell state. Here, we define DNA-methylation changes that accompany metastatic progression in melanoma patients and discover Nuclear Receptor Subfamily 2 Group F, Member 2 – isoform 2 (NR2F2-Iso2) as an epigenetically regulated metastasis driver. NR2F2-Iso2 is transcribed from an alternative transcriptional start site (TSS) and it is truncated at the N-terminal end which encodes the NR2F2 DNA-binding domain. We find that NR2F2-Iso2 expression is turned off by DNA methylation when NCCs differentiate into melanocytes. Conversely, this process is reversed during metastatic melanoma progression, when NR2F2-Iso2 becomes increasingly hypomethylated and re-expressed. Our functional and molecular studies suggest that NR2F2-Iso2 drives metastatic melanoma progression by modulating the activity of full-length NR2F2 (Isoform 1) over EMT- and NCC associated target genes. Our findings indicate that DNA-methylation changes play a crucial role during metastatic melanoma progression, and their control of NR2F2 activity allows transformed melanocytes to acquire NCC-like and EMT-like features. This epigenetically regulated transcriptional plasticity facilitates cell state transitions and metastatic spread.
2022-12-31 | GSE213382 | GEO
Project description:Melanoma is a highly metastatic tumor type responsible of the large majority of the skin cancer-related deaths. Melanoma cells recapitulate the migratory and invasive nature of neural crest stem cells from which melanocytes arise. However, the mechanisms by which these developmental programs confer melanoma cells with more aggressive properties are not understood. Here we provide evidence for an epigenetically regulated developmental program that is aberrantly re-activated by melanoma cells to aid in the metastatic process. We reasoned that studying molecular changes occurring during the ontogeny of melanocytes from progenitor neural crest cells (NCC), and identifying developmental programs retained or re-gained by melanoma cells, could reveal crucial processes that modulate melanoma aggressiveness. Here we describe a novel mechanism that controls the activity of a transcriptional regulator of human neural crest, the Nuclear Receptor Subfamily 2 Group F, Member 2 (NR2F2). We find that highly localized DNA methylation acts as an on/off switch that controls the expression of a truncated NR2F2 isoform (NR2F2-Iso2) from an alternative transcription start site during NCC to melanocyte differentiation. We show that melanoma cells co-opt this developmental program by decreased DNA methylation and re-expression of NR2F2-Iso2 to promote melanoma metastasis. NR2F2-Iso2 regulates the transcriptional activity of the full length NR2F2 isoform 1 by impairing its binding to chromatin, which results in altered expression of NCC and differentiation genes. Our data demonstrate that epigenetic reactivation of NR2F2 isoform 2 promotes melanoma metastasis, which could be targeted for therapeutic purposes.
2023-02-12 | GSE102553 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:An epigenetic switch controls the expression of an alternative NR2F2 isoform that unleashes a pro-metastatic program in melanoma
| PRJNA397989 | ENA