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Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells

ABSTRACT: Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells

PROVIDER: PRJNA491367 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7826320.fastq.gz	Fastqsanger.gz
	SRR7826330.fastq.gz	Fastqsanger.gz
	SRR7826340.fastq.gz	Fastqsanger.gz
	SRR7826350.fastq.gz	Fastqsanger.gz
	SRR7826321.fastq.gz	Fastqsanger.gz

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Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells [RNA-seq]

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Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells [RNA-seq]

Project description:Abnormal differentiation contributes to the spectrum of aberrant properties of tumor cells. Differentiation of both normal and tumor cells is controlled by regulatory networks enforced by transcription factors (TFs) involved in lineage specification. Among them, pioneer factors such as FOXA1/2, are able to bind and make accessible naïve chromatin, thus critically contributing to the establishment of gene regulatory networks. Pancreatic ductal adenocarcinoma (PDAC) is characterized by massive heterogeneity, with the coexistence at all disease stages of well- and poorly-differentiated cells with diverging transcriptional networks. We found that FOXA2, a TF controlling pancreas specification, was expressed in both well- and poorly-differentiated PDAC cells, but it controlled distinct gene expression programs and displayed extensively different genomic distributions because of its partnership with TFs expressed in a differentiation grade-specific manner, such as HNF1 and HOXB8/9 in well- and poorly-differentiated cells, respectively. These data suggest that pioneer TFs such as FOXA2 are versatile transcriptional regulators whose broad contribution to the gene regulatory networks of highly heterogeneous cancers such as PDACs, depends on the differential availability of partner TFs expressed in distinct tumor cells.

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Cell differentiation grade determines distinct FOXA2 contributions to the cis-regulatory networks of pancreatic cancer cells

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

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Gene expression profile of Huh7 cells upon knock-down of FOXA2 or FOXA2-DS-S

Project description:We used siRNAs to knock-down the gene FOXA2 and the positionally-conserved ncRNA (pcRNA) FOXA2-DS-S is Huh7. We have shown that FOXA2 regulates its own expression by binding its promoter, but it can also affect the expression of the associated pcRNA FOXA2-DS-S. At the same time, we have shown that FOXA2-DS-S is necessary for the expression of the FOXA2 gene. These data suggest that the pcRNA acts locally, in cis, to regulate the expression of FOXA2. With this microarray experiment with aimed to explore further the genome-wide transcriptional effects of FOXA2-DS-S or FOXA2 knock-down.

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