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The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis

ABSTRACT: The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis

PROVIDER: PRJNA807688 | ENA |

REPOSITORIES: ENA

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The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [ChIP-seq]

Project description:The contribution of epigenetic dysregulation to metastasis remains understudied. Through a meta-analysis of gene expression datasets followed by a mini-screen, we identified PHF8, a histone demethylase of the Jumonji C protein family, as a novel pro-metastatic gene in melanoma. Loss- and gain-of-function approaches demonstrate that PHF8 promotes cell invasion without affecting proliferation in vitro, and increases dissemination but not sub-cutaneous tumor growth in vivo, thus supporting its specific contribution to the acquisition of metastatic potential. PHF8 requires its histone demethylase activity to enhance melanoma cell invasion. Transcriptomic and epigenomic analyses revealed that PHF8 orchestrates a molecular program that directly controls the TGFβ signaling pathway and as a consequence, melanoma invasion and metastasis. Our findings bring a mechanistic understanding of epigenetic regulation of metastatic fitness in cancer, which may pave the way for improved therapeutic interventions.

2022-02-23 | GSE196897 | GEO

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [RNA-seq]

2022-02-23 | GSE196905 | GEO

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [ChIP-seq]

Project description:The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [ChIP-seq]

| PRJNA807678 | ENA

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [RNA-seq]

Project description:The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis [RNA-seq]

| PRJNA807691 | ENA

The histone demethylase PHF8 is essential for cytoskeleton dynamics

Project description:PHF8 is a histone demethylase associated with X-linked mental retardation (XLMR). It has been described as a transcriptional coactivator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 controls the expression of genes involved in cell adhesion and cytoskeleton organization such as RhoA, Rac1 and GSK3M-NM-2. A lack of PHF8 not only results in a cell cycle delay but also in a disorganized actin cytoskeleton and impaired cell adhesion. Our data demonstrate that PHF8 directly regulates the expression of these genes by demethylating H4K20me1 at promoters. Moreover, c-Myc transcription factor interacts with PHF8 and binds to the analyzed promoters, suggesting that c-Myc is involved on PHF8 recruitment to these promoters. Further analysis in the neuroblastoma cell line SH-SY5Y and in cortical neurons shows that depletion of PHF8 results in deficient neurite elongation. Overall, our results suggest that the mental retardation phenotype associated with loss of function of PHF8 could be due to abnormal neuronal connections as a result of alterations in cytoskeleton function. HeLa cells were transfected with either control or PHF8 siRNAs. Experiments were performed in biological triplicates. RNA were extracted and sujected to microarray analysis.

2012-07-31 | E-GEOD-38175 | biostudies-arrayexpress

The histone demethylase PHF8 is essential for cytoskeleton dynamics

Project description:PHF8 is a histone demethylase associated with X-linked mental retardation (XLMR). It has been described as a transcriptional coactivator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 controls the expression of genes involved in cell adhesion and cytoskeleton organization such as RhoA, Rac1 and GSK3β. A lack of PHF8 not only results in a cell cycle delay but also in a disorganized actin cytoskeleton and impaired cell adhesion. Our data demonstrate that PHF8 directly regulates the expression of these genes by demethylating H4K20me1 at promoters. Moreover, c-Myc transcription factor interacts with PHF8 and binds to the analyzed promoters, suggesting that c-Myc is involved on PHF8 recruitment to these promoters. Further analysis in the neuroblastoma cell line SH-SY5Y and in cortical neurons shows that depletion of PHF8 results in deficient neurite elongation. Overall, our results suggest that the mental retardation phenotype associated with loss of function of PHF8 could be due to abnormal neuronal connections as a result of alterations in cytoskeleton function.

2012-08-01 | GSE38175 | GEO

Histone demethylase PHF8 promotes prostate cancer metastasis via the E2F1-SNAI1 axis.

Project description:RNA-seq analysis were applied to elucidate the transcriptional differences between PC-3 cell lines transfected with control-sgRNA (Control) and PHF8-shRNA (PHF8-KD). a total of 1122 DEGs were identified with 775 upregulated and 347 downregulated genes (FDR<0.05, |log2FoldChanges|>1)

2024-09-11 | GSE241799 | GEO

The histone demethylase PHF8 regulates TGFβ signaling and promotes melanoma metastasis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-22 | GSE196906 | GEO

Genome-wide identification of target genes for the histone demethylase Phf8 in the oligodendroglial cell line CG4 [Phf8KO]

Project description:To identify target genes of the histone demethylase Phf8 in oligodendroglial cells in a genome-wide and unbiased approach, RNA-sequencing studies were performed on wildtype CG4 cells and CRISPR/Cas9-edited Phf8 knockout cell lines. We compared three wildtype and one CRISPR/Cas9-treated clone without genome editing with four CRISPR/Cas9 Phf8-knockout clones. Among others we detected substantial changes in the expression of genes associated with cell cycle and replication of DNA.

2024-04-12 | GSE253877 | GEO

ChIP-seq of PHF8 and H3K4me3

Project description:PHF8 is an H3K9me2 demethylase, interacts with H3K4me3 and RNA Polymerase II, is enriched at thousands of transcription start sites and can act as a transcriptional co-activator. ChIP-seq of PHF8 in HeLa, 293T and Hs68 cells, and of H3K4me3 in Hs68 fibroblasts was performed. Normal IgG-IP or input DNA served as negative controls.

2010-04-27 | E-GEOD-20725 | biostudies-arrayexpress

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