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Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells

ABSTRACT: Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells

PROVIDER: PRJNA824445 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18674500_1.fastq.gz	Fastqsanger.gz
	SRR18674500_2.fastq.gz	Fastqsanger.gz
	SRR18674501_1.fastq.gz	Fastqsanger.gz
	SRR18674501_2.fastq.gz	Fastqsanger.gz
	SRR18674502_1.fastq.gz	Fastqsanger.gz

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Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells [ChiP-seq]

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Transcription factor Creb3l1 maintains proteostasis in neuroendocrine cells [RNA-seq]

Project description:We have shown that the expression of the endoplasmic reticulum stress sensor Creb3l1 increases in magnocellular neurones (MCNs) in the rat hypothalamus in response to increased physiological demands for protein synthesis. Here we adopted a multiomic strategy to investigate specific roles of Creb3l1 in MCN homeostasis. We first performed chromatin immunoprecipitation followed by genome sequencing (ChIP-seq) to identify Creb3l1 genomic targets in the water deprived MCN enriched hypothalamic preparation. We then compared ChIP-seq gene targets with water deprived and Creb3l1 knockdown supraoptic nucleus RNA sequencing transcriptome datasets. This has provided an integrated signalling-gene regulation network for this transcription factor illuminating changes to cell pathways and function, an approach that has led us to understand the physiological changes that occur in MCNs to cope with excessive protein demands.

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Knockdown of transcription factor Creb3l1 in anterior pituitary mouse corticotroph cell line AtT20

Project description:Transcription factor Creb3l1 is a non-classical ER stress molecule that is emerging as an important component for cellular homeostasis, particularly within cell-types with high peptide secretory capabilities. We have previously shown that Creb3l1 serves an important role in body fluid homeostasis through its transcriptional control of the gene coding for antidiuretic hormone arginine vasopressin in the neuropeptide rich magnocellular neurons of the supraoptic nucleus. To identify other genes regulated by transcription factor Creb3l1 in secretory cells, we performed RNA-sequencing of Creb3l1 knockdown anterior pituitary mouse corticotroph cell line AtT20.

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Project description:The unfolded protein response (UPR) is activated in response to hypoxia-induced stress such as in the tumor microenvironment. This study examined the role of CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the UPR, in breast cancer development and metastasis. Initial experiments identified the loss of CREB3L1 expression in metastatic breast cancer cell lines compared to low- or non-metastatic cell lines. When metastatic cells were transfected with CREB3L1 they demonstrated reduced invasion and migration in vitro, as well as a significantly decreased ability to survive under non-adherent or hypoxic conditions. Interestingly, in an in vivo rat mammary tumor model, CREB3L1 expressing cells not only failed to form metastases compared to CREB3L1 null cells but regression of the primary tumors was seen in 70% of the animals as a result of impaired angiogenesis. Microarray and ChIP on Chip analyses identified changes in the expression of many genes involved in cancer development and metastasis, including a decrease in those involved in angiogenesis. These data suggest that CREB3L1 plays an important role in suppressing tumorgenesis and loss of expression is required for the development of a metastatic phenotype. CREB3L1 is a member of the unfolded protein response family of proteins. CREB3L1 expression is lost from metastatic breast cancer cells. We wanted to determine the promoters of genes that CREB3L1 bound to.

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