Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BORIS/CTCFL-mediated chromatin accessibility alterations promote a pro-invasive transcriptional signature in melanoma cells

ABSTRACT: Melanoma is the deadliest form of skin cancer, due to its tendency to metastasize early. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcription regulator that becomes ectopically expressed in melanoma. We recently showed that BORIS contributes to melanoma phenotype switching by altering the gene expression program of proliferative melanoma cells in favor of a more invasive phenotype. However, how BORIS alters the transcriptome remains unclear. Here, ATAC-seq was used to study BORIS-mediated chromatin accessibility alterations in proliferative melanoma cells. Genes that gained promoter accessibility following ectopic BORIS expression, were enriched for melanoma-specific invasive genes as well as invasion-associated biological processes, while promoters of genes associated with proliferation show reduce accessibility. Integration of ATAC-Seq and RNA-Seq data demonstrates that increased chromatin accessibility is associated with transcriptional upregulation of genes involved in tumor progression processes, and the aberrant activation of oncogenic transcription factors, while reduced chromatin accessibility and downregulated genes, were associated with repressed activity of tumor suppressors. Together, these findings indicate that BORIS mediates transcriptional reprogramming in melanoma cells by altering chromatin accessibility and gene expression, shifting the cellular transcription landscape of proliferative melanoma cells towards a pro-invasive genetic signature.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211800 | GEO | 2023/04/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq analysis of doxycycline-inducible BORIS/CTCFL expression in the metastatic melanoma cell line MM057

Project description:Brother of Regulator of Imprinted Sites (BORIS) is a DNA binding protein with high similarity to CCCTC binding factor (CTCF), a multifunctional transcription factor that plays an important role in genome organization. Like CTCF, BORIS plays a role in transcriptional regulation. BORIS becomes aberrantly expressed in melanoma with a higher frequency in metastatic tumors compared to primary tumors, which indicates a role for BORIS in melanoma progression. Currently, little is known about the role of BORIS in melanoma. To gain insight into the functional role of BORIS in melanoma we established doxycycline-inducible BORIS expression in the MM057 melanoma cell line that harbors a proliferation-associated transcriptome. Next, we used RNA-seq to investigate BORIS-mediated transcriptional changes. We show that differentially expressed genes are enriched among invasion-related processes and gene signatures, indicating that BORIS expression contributes to an EMT-like switch from a proliferation to invasion-associated transcriptome. In agreement with these findings, we demonstrate that BORIS overexpression leads to reduced proliferation and increased migration and invasion. Taken together, these data indicate that expression of BORIS promotes a switch from a proliferative to invasive state at both the transcriptional and phenotypic level in melanoma cell lines.

2020-01-01 | GSE126807 | GEO

HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis

Project description:Melanomas are heterogeneous and adopt multiple transcriptional states that can confer an invasive phenotype and resistance to therapy. Little is known about the epigenetic drivers of these cell states, limiting our ability to regulate melanoma heterogeneity and tumor progression. Here we identify stress-induced HDAC8 activity as the driver of a transcriptional state that increased the formation of melanoma brain metastases (MBM). Exposure of melanocytes and melanoma cells to multiple different stresses led to HDAC8 activation, a switch to a gene expression signature associated with a neural crest-stem cell like state (NCSC) and the adoption of an amoeboid, invasive phenotype. This cell state enhanced the survival of melanoma cells under shear stress conditions and increased the formation of metastases in the brain. ATAC-Seq and ChIP-Seq analysis showed HDAC8 to alter chromatin structure by increasing H3K27ac and accessibility at c-Jun binding sites without changing global histone acetylation. The increased accessibility of Jun binding sites was paralleled by decreased H3K27ac and accessibility at MITF binding sites and loss of melanoma-lineage gene expression. Mass spectrometry-based acetylomics demonstrated that HDAC8 deacetylated the histone acetyltransferase (HAT) EP300 leading to its enzymatic inactivation. This, in turn, led to an increased binding of EP300 to Jun-transcriptional sites and decreased binding to MITF-transcriptional sites. Increased expression of EP300 decreased invasion and increased the sensitivity of melanoma cells to multiple stresses while inhibition of EP300 function increased invasion, resistance to stress and the development of MBM. We identified HDAC8 as a novel mediator of transcriptional co-factor inactivation and chromatin accessibility that increases MBM development.

2023-09-26 | PXD044471 | Pride

Effect of extracellular S100A4 on melanoma cells of different phenotypes

Project description:S100A4 is a known metastasis-promoting factor, rich in the tumor microenvironment. To clarify how extracellular S100A4 execute its pro-metastatic function, we analyzed gene expression in melanoma cells stimulated with recombinant protein rS100A4 and compared it to the expression in control non-stimulated cells. Two melanoma cell lines representing two distinct phenotypes M-bM-^@M-^S invasive (Melmet 1) and non-invasive/proliferative (Melmet 5) M-bM-^@M-^S were included in the study. The response at the gene expression level was much stronger in Melmet 5 than in Melmet 1. Melmet 5 down-regulated genes associated with melanocytic differentiation, indicating that Melmet 5 cells gained dedifferentiated, more invasive phenotype after stimulation with rS100A4. The observed changes in the expression of metabolism associated genes suggested the occurrence of metabolic reprogramming. We conclude that extracellular S100A4 stimulate the transition to the invasive phenotype in poorly-invasive melanoma cells, and that this transition is associated with metabolic reprogrammingve Total RNA was isolated from Melmet 1 and Melmet 5 cells stimulated with rS100A4 protein for 48hrs compared to non-stimulated cells.

2015-02-13 | E-GEOD-65897 | biostudies-arrayexpress

Effect of extracellular S100A4 on melanoma cells of different phenotypes

Project description:S100A4 is a known metastasis-promoting factor, rich in the tumor microenvironment. To clarify how extracellular S100A4 execute its pro-metastatic function, we analyzed gene expression in melanoma cells stimulated with recombinant protein rS100A4 and compared it to the expression in control non-stimulated cells. Two melanoma cell lines representing two distinct phenotypes – invasive (Melmet 1) and non-invasive/proliferative (Melmet 5) – were included in the study. The response at the gene expression level was much stronger in Melmet 5 than in Melmet 1. Melmet 5 down-regulated genes associated with melanocytic differentiation, indicating that Melmet 5 cells gained dedifferentiated, more invasive phenotype after stimulation with rS100A4. The observed changes in the expression of metabolism associated genes suggested the occurrence of metabolic reprogramming. We conclude that extracellular S100A4 stimulate the transition to the invasive phenotype in poorly-invasive melanoma cells, and that this transition is associated with metabolic reprogrammingve

2015-02-13 | GSE65897 | GEO

ATAC-seq of human oesophageal adenocarcinoma KYAE1 cell line treated with lapatinib

Project description:To investigate initial changes to chromatin accessibility associated with resistance to lapatinib, we performed ATAC-seq on KYAE1 cells treated with 500 nM lapatinib for 24 hours and vehicle control (DMSO) for 24 hours.

2022-09-26 | E-MTAB-10310 | biostudies-arrayexpress

ATAC-seq of human gastric adenocarcinoma NCI-N87 cell line treated with lapatinib

Project description:To investigate initial changes to chromatin accessibility associated with resistance to lapatinib, we performed ATAC-seq on NCI-N87 cells treated with 250nM lapatinib for 24 hours and vehicle control (DMSO) for 24 hours.

2022-09-26 | E-MTAB-10313 | biostudies-arrayexpress

ATAC-seq of human oesophageal adenocarcinoma WTSI-OESO_009 (CAM408) organoid treated with lapatinib

Project description:To investigate initial changes to chromatin accessibility associated with resistance to lapatinib, we performed ATAC-seq on WTSI-OESO_009 cells treated with 1000 nM lapatinib for 24 hours and vehicle control (DMSO) for 24 hours.

2022-09-26 | E-MTAB-10306 | biostudies-arrayexpress

ATAC-seq of human oesophageal adenocarcinoma OE19 cell line treated with lapatinib

Project description:To investigate changes to chromatin accessibility associated with resistance to lapatinib, we performed ATAC-seq on OE19 cells treated with 500 nM lapatinib for 1, 7 and 35 days and vehicle control (DMSO) for 1 day.

2022-09-26 | E-MTAB-10302 | biostudies-arrayexpress

CDK9 inhibition with AZD4573 in DLBCL

Project description:We report the effects of CDK9 inhibition (AZD4573) on the epigenetic landscape in Diffuse Large B-cell Lymphoma (DLBCL). This study utilized the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess genome-wide chromatin accessibility in two DLBCL cell lines, OCI-LY3 and VAL, treated with AZD4573 (30 nM) at 0, 3, and 8 hours. We found that CDK9 inhibition led to gain and loss of accessible chromatin genome-wide, with enrichment of CTCF/BORIS motifs in decreased accesibility regions.

2022-03-21 | GSE198851 | GEO

Genetic determinants of chromatin accessibility in T cell activation across human individuals [RNA-seq]

Project description:We analyzed 105 chromatin accessibility (ATAC-seq) profiles in activated primary CD4+ T cells from healthy donors to identify genetic variants associated with variability in chromatin accessibility (ATAC-QTLs).we analyzed 105 chromatin accessibility (ATAC-seq) profiles in activated primary CD4+ T cells from healthy donors to identify genetic variants associated with variability in chromatin accessibility (ATAC-QTLs)

2018-07-12 | GSE86887 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data