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Cell-autonomous transcriptional mechanism for enhancement of translation capacity in secretory cells

ABSTRACT: Cell-autonomous transcriptional mechanism for enhancement of translation capacity in secretory cells

PROVIDER: PRJNA547597 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9211840_1.fastq.gz	Fastqsanger.gz
	SRR9211840_2.fastq.gz	Fastqsanger.gz
	SRR9211850_1.fastq.gz	Fastqsanger.gz
	SRR9211850_2.fastq.gz	Fastqsanger.gz
	SRR9211860_1.fastq.gz	Fastqsanger.gz

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Project description:Translation is a basic cellular process and its capacity is adapted to cell function. In particular, secretory cells achieve high protein synthesis levels without triggering the protein stress response. It is unknown how and when translation capacity is increased during differentiation. Here, we show that the transcription factor Creb3l2 is a scaling factor for translation capacity in pituitary secretory cells and that it directly binds ~75% of regulatory and effector genes for translation. In parallel with this cell-autonomous mechanism, implementation of the physiological UPR pathway prevents triggering the protein stress response. The pituitary differentiation factor Tpit activates Creb3l2 expression, the Creb3l2-dependent regulatory network as well as the physiological UPR pathway. Thus, Creb3l2 implements high basal translation levels through direct targeting of translation effector genes acting downstream of signaling pathways that otherwise regulate protein synthesis. Expression of Creb3l2 may be a useful means to enhance production of therapeutic proteins.

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Cell-autonomous transcriptional mechanism for enhancement of translation capacity in secretory cells

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

2019-07-29 | GSE132324 | GEO

UV induced translation capacity is developmentaly regulated in fungi

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The CrebA/Creb3-like transcription factors are major and direct regulators of secretory capacity

Project description:Abstract: Secretion occurs in all cells, with relatively low levels in most cells and extremely high levels in specialized secretory cells, such as those of the pancreas, salivary and mammary glands. Here, we report that the CrebA/Creb3-like family of bZip transcription factors functions to upregulate expression of both the general protein machinery required in all cells for secretion and of cell-type specific secreted proteins. Drosophila CrebA directly binds the enhancers of secretory pathway genes and is both necessary and sufficient to activate expression of every secretory pathway component gene examined thus far. Microarray profiling reveals that CrebA also upregulates expression of genes encoding cell type specific secreted components. Finally, we find that the human CrebA orthologues, Creb3L1 and Creb3L2, have the ability to upregulate the secretory pathway in non-secretory cell types. This SuperSeries is composed of the following subset Series: GSE23334: Active Creb3L1 can upregulate secretory pathway genes in HeLa cells GSE23346: CrebA is a major and direct regulator of secretory pathway gene expression Refer to individual Series

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CrebA regulation of secretory capacity: Genome-wide transcription profiling coupled with in vivo DNA binding studies

Project description:DNA binding assays, expression analyses, and binding site mutagenesis revealed that the Drosophila CrebA transcription factor (TF) boosts secretory capacity in the embryonic salivary gland (SG) through direct regulation of secretory pathway component genes (SPCGs). The mammalian orthologues of CrebA, the Creb3L-family of leucine zipper TFs, not only activate SPCG expression in a variety of mammalian tissues but can also activate SPCG expression in Drosophila embryos, suggesting a highly conserved role for this family of proteins in boosting secretory capacity. However, in vivo assays reveal that CrebA binds far more genes than it regulates, and it remains unclear what distinguishes functional binding. It is also unclear if CrebA is the major factor driving SPCG gene expression in all Drosophila embryonic tissues and/or if CrebA also regulates other tissue-specific functions. Thus, we did single cell RNA sequencing (scRNA-seq) of wild-type (WT) and CrebA null embryos to explore the relationship between CrebA binding and gene regulation. We find that CrebA binds the proximal promoters of its targets, that SPCGs are the major class of genes regulated by CrebA across tissues, and that CrebA is sufficient to activate SPCG expression even in cells that do not normally express the protein. A comparison of scRNA-Seq to other methods for capturing regulated transcripts reveals that the different methodologies identify overlapping but distinct sets of CrebA targets.

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