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Identification of human genes of which expression are induced by 4MU-xyloside treatment

ABSTRACT: The Golgi stress response is a homeostatic mechanism that augments the functional capacity of the Golgi apparatus when Golgi function becomes insufficient (Golgi stress). Three response pathways of the Golgi stress response have been identified in mammalian cells, the TFE3, HSP47 and CREB3 pathways, which augment the capacity of specific Golgi functions such as N-glycosylation, anti-apoptotic activity and pro-apoptotic activity, respectively. On the contrary, glycosylation of proteoglycans (PGs) is another important function of the Golgi, although the response pathway upregulating expression of glycosylation enzymes for PGs in response to Golgi stress remains unknown. Here, we found that expression of glycosylation enzymes for PGs was induced upon insufficiency of PG glycosylation capacity in the Golgi (PG-Golgi stress), and that transcriptional induction of genes encoding glycosylation enzymes for PGs was independent of the known Golgi stress response pathways and ER stress response. Promoter analyses of genes encoding these glycosylation enzymes revealed the novel enhancer element PGSE, which regulates their transcriptional induction upon PG-Golgi stress. From these observations, the response pathway we discovered is a novel Golgi stress response pathway, which we have named the PG pathway.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117938 | GEO | 2018/08/01

REPOSITORIES: GEO

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Project description:Secondary metabolites play a key role in coordinating ecology and defense strategies of plants. Diversity of these metabolites arise by conjugation of core structures with diverse chemical moieties, such as sugars in glycosylation. Active pools of phytohormones, including those involved in plant stress response are also regulated by glycosylation. While, much is known about the enzymes involved in glycosylation, we know little about their regulation or coordination with other processes. We characterized the flavonoid pathway transcription factor, TRANSPARENT TESTA 8 (TT8) in Arabidopsis thaliana, using an integrative omics strategy. This approach provides a systems level understanding of the cellular machinery that is used to generate metabolite diversity by glycosylation. Metabolomics analysis of TT8 loss-of-function and inducible overexpression lines showed that TT8 coordinates glycosylation of not only flavonoids, but also nucleotides, thus, implicating TT8 in regulating pools of activated nucleotide sugars. Transcriptome and promoter network analyses revealed that TT8 regulome included sugar transporters, proteins involved in sugar binding and sequestration, and a number of carbohydrate active enzymes. Importantly, TT8 affects stress response, along with brassinosteroid and jasmonic acid biosynthesis, by directly binding to the promoters of key genes of these processes. This combined effect on metabolites glycosylation and stress hormones by TT8 inducible overexpression led to significant increase in tolerance towards multiple abiotic and biotic stresses. Conversely, loss of TT8 leads to increased sensitivity to these stresses. Thus, the transcription factor TT8 is an integrator of secondary metabolism and stress response. These findings provide novel approaches to improve broad-spectrum stress tolerance. Gene expression analysis for 6-day old Arabidopsis thaliana seedling were performed for TT8 loss-of-function line, tt8-3 (in Ws background), and its wild type background control, Ws. Two independent biological replicates for each line were hybridized onto two slides of Agilent SurePrint G2 Agilent Arabidopsis V4 (4x44K), with each slide having two technical replicates for each line. Contributors: Amit Rai, Shivshankar Umashankar, Megha, Lim Boon Kiat, Johanan Aow Shao Bing, Sanjay Swarup.

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Identification of human genes of which expression are induced by 4MU-xyloside treatment

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