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PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [RNA-seq]

ABSTRACT: PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [RNA-seq]

PROVIDER: PRJNA938748 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23619074.fastq.gz	Fastqsanger.gz
	SRR23619075.fastq.gz	Fastqsanger.gz
	SRR23619076.fastq.gz	Fastqsanger.gz
	SRR23619077.fastq.gz	Fastqsanger.gz
	SRR23619078.fastq.gz	Fastqsanger.gz

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PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [RNA-seq]

Project description:The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors and transcriptional regulators converge to be regulated. Specific associations of PML and PML-NBs with chromatin are described in different cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in a cellular context where it regulates relevant phenotypes is still lacking.We examined the role of PML in chromatin association and transcription in triple-negative breast cancer (TNBC), a pathological condition where PML exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a cell type-relevant function of transcriptional regulation. PML also plays an indirect regulatory function in TBNC cells by promoting the expression of pro-metastatic genes outside PADs.Our findings demonstrate that PML is an important transcriptional regulator of metastasis and pro-oncogenic metagenes in TNBC cells, via distinct molecular activities that include indirect transcriptional regulation and direct epigenetic organization of heterochromatin domains that embed regions of localized transcriptional activity.

2023-09-11 | GSE226111 | GEO

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ChIP-seq]

2023-09-11 | GSE226060 | GEO

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ATAC-seq]

2023-09-11 | GSE240309 | GEO

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer

Project description:PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer

| PRJNA939167 | ENA

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ATAC-seq]

Project description:PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ATAC-seq]

| PRJNA1003122 | ENA

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ChIP-seq]

Project description:PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [ChIP-seq]

| PRJNA938442 | ENA

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer.

Project description:The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in cellular contexts where it promotes relevant phenotypes is still lacking. We examined PML chromatin association in triple-negative breast cancer (TNBC) cell lines, where it exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain discrete gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a relevant gene regulatory function. We also find that PML plays indirect regulatory roles in TNBC cells by promoting the expression of pro-metastatic genes outside PADs. Our findings suggest that PML is an important transcriptional regulator of pro-oncogenic metagenes in TNBC cells, via transcriptional regulation and epigenetic organization of heterochromatin domains that embed regions of local transcriptional activity.

| S-EPMC10639071 | biostudies-literature

PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer

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

2023-09-07 | GSE226210 | GEO

OCT-2 is associated with pro-metastatic epigenomic properties of triple-negative breast cancer cells

Project description:OCT-2 is associated with pro-metastatic epigenomic properties of triple-negative breast cancer cells

| PRJNA1236320 | ENA

PML regulates PPAR signaling and fatty acid oxidation in breast cancer

Project description:Cancer cells exhibit an aberrant metabolism which facilitates more efficient production of biomass, and hence tumor growth and progression. The genetic cues modulating this metabolic switch remain largely undetermined, however. Here we identify a metabolic function for PML which reveals an unexpected role for this bona-fide tumor suppressor in pro-survival activity in breast cancer. We find that PML acts as both a negative regulator of PGC1A acetylation and as a potent activator of peroxisome proliferator-activated receptor (PPAR) signaling and fatty acid oxidation (FAO). We further show that as FAO PML promotes ATP production, inhibits anoikis, and allows luminal filling in 3D basement membrane breast culture models. Furthermore, analysis of breast cancer biopsies reveals that PML is over-expressed in a subset of breast cancers, and is enriched in triple-negative cases. Indeed, PML expression in breast cancer correlates strikingly with reduced time to recurrence, a gene signature of poor prognosis and activated PPAR signaling. These findings have important therapeutic implications, as PML and its key role in FAO metabolism are amenable to pharmacological suppression as a mode of cancer prevention and treatment. Mouse livers from Pml-WT and Pml-KO mice were harvested after 20 week diet with high fat diet (60% Cal from fat; Harlan 06414) or control diet (10% Cal from fat; Harlan 08806). Mice were fasted for 8h prior to tissue harvesting in order to avoid the effect of immediate food intake. 3 tissue extracts per genotype and condition were analyzed (out of a total of 8 mice per group).

2013-01-29 | E-GEOD-39220 | biostudies-arrayexpress

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