The transcriptional response to MESH1 silencing
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ABSTRACT:
PROVIDER: PRJNA558557 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:All organisms are exposed to various stresses, necessitating adaptive strategies for survival and homeostasis. In bacteria, the main stress-coping mechanism is stringent response triggered by the accumulation of the “alarmone” (p)ppGpp to trigger proliferation arrest and transcriptional reprogramming. Mammalian genomes encode MESH1 —the homologue of the (p)ppGpp hydrolase SpoT, with unknown function. Therefore, we used microarrays to determine the transcriptional response to MESH1 silencing.
2022-08-31 | GSE135358 | GEO
Project description:MESH1 encodes for Metazoan SpoT Homolog 1, which is a homologue of bacterial SpoT that mediates bacterial stringent response. In human cells, we found that MESH1-silencing induces an extensive transcriptional response in clear cell carcinoma cell line RCC4 that partially overlap with mammalian cell integrated stress response (ISR), which ATF4 up-regulation is an essential branch of the response. In this study, the goal is to elucidate the role of ATF4 up-regulation in MESH1-silencing transcriptional response.
2021-07-30 | GSE114128 | GEO
Project description:TAZ is an important transcriptional co-activator involved in the HIPPO pathway that regulates cell growth, tumorigenesis and organ development and can play as a key mediator in other signaling pathways, such as MESH1-regulated pathways. MESH1 is the human ortholog of spoT that regulates sringent response in bacteria. MESH1 silencing inhibits cell proliferation and triggers a genome-wide transcriptional reprogramming as how spoT works in bacteria, among which TAZ is significantly down-regulated. Therefore, we aim to investigate how much TAZ contributes to the MESH1-regulated gene signature. We performed this microarray restoring TAZ level upon MESH1 silencing and measured the rescue effect. Overall, approximately 30% of the MESH1 regulated genes (up or down-regulated by siMESH1 by at least 2 folds) were rescued by the TAZ overexpression by at least 1.5 folds. Interestingly, a series of cell cycle related genes (RRM1, RRM2,CDK1 and CDC6) were rescued by TAZ restoration, suggesting that TAZ is an important mediator involved in the MESH1-regulated pathway to trigger the downstream tarnscriptomic reprogramming and cell proliferation inhibition. By understanding the mechanisms of MESH1 and its regulated pathways, we may disclose a new target for cancer therapy to regulate cancer cell growth. We used microarrays to detail the coverage of TAZ regulated genes downstream to MESH1 regulated gene signature in H1975 cells.
2022-07-23 | GSE135346 | GEO
Project description:Nutrient deprivation triggers stringent response in bacteria, allowing rapid reallocation of resources from proliferation toward stress survival. Critical to this process is the accumulation of (p)ppGpp regulated by the RelA/SpoT homologues. While mammalian genomes encode MESH1—the homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Therefore, the function of MESH1 remains a mystery. Here, we report that genetic removal of MESH1 from human cell induce an extensive transcriptional response. The changes are distinct from the canonical unfolding protein response but strongly resemble the bacterial stringent response, which induce cell proliferation arrest, implicating MESH1 in a previously uncharacterized stress response in human cells.
2020-01-26 | GSE114282 | GEO
Project description:All organisms are constantly exposed to various stresses, necessitating adaptive strategies for survival. In bacteria, the main stress-coping mechanism is the stringent response triggered by the accumulation of “alarmone” (p)ppGpp to arrest proliferation and reprogram transcriptome. While mammalian genomes encode MESH1—the homolog of the (p)ppGpp hydrolase SpoT, current knowledge about its function remains limited. We found MESH1 expression tended to be higher in tumors and associated with poor patient outcomes. Consistently, MESH1 knockdown robustly inhibited proliferation, depleted dNTPs, reduced tumor sphere formation, and retarded xenograft growth. These antitumor phenotypes associated with MESH1 knockdown were accompanied by a significantly altered transcriptome, including the repressed expression of TAZ, a HIPPO coactivator, and proliferative gene. Importantly, TAZ restoration mitigated many anti-growth phenotypes of MESH1 knockdown, including proliferation arrest, reduced sphere formation, tumor growth inhibition, dNTP depletion, and transcriptional changes. Furthermore, TAZ repression was associated with the histone hypo-acetylation at TAZ regulatory loci due to the induction of epigenetic repressors HDAC5 and AHRR. Together, MESH1 knockdown in human cells altered the genome-wide transcriptional patterns and arrested proliferation that mimicked the bacterial stringent response through the epigenetic repression of TAZ expression.
2022-03-12 | GSE147062 | GEO
Project description:Expression profile of MESH1 and ATF4 silencing RCC4 cells
| PRJNA464382 | ENA
Project description:Transcriptional profile of MESH1-silenced RCC4 cells
| PRJNA470796 | ENA
Project description:TAZ overexpression partially rescued the transcriptomic reprogramming triggered by MESH1 silencing
| PRJNA558540 | ENA
Project description:Keratinocyte response to SNHG26 silencing
| PRJNA895451 | ENA
Project description:MESH1 is the metazoan homolog of bacterial SpoT, the main phosphatase that dephosphorylates and degrades (p)ppGpp, the alarmone involved in the bacterial stringent response. The functional role of MESH1 in human cells is unknown. To define the global transcriptional response to MESH1 knockdown, we employed microarrays to perform transcriptome analysis of H1975 when the MESH1 was knocked down using three independent siRNAs targeting MESH1. The changes of each gene were derived by zero-transformation, followed by filtering to derive the genes affected by MESH1 knockdown. These datasets showed the transcriptional features of the mammalian stringent response and identified a prominent TAZ repression. Thus, we performed a second experiment to determine the contribution of TAZ repression to the transcriptional response of MESH1 knockdown by comparing the effects of MESH1-knockdown gene signatures in H1975 cells transduced with control or constitutive active TAZ (TAZS89A). The transcriptional response of these two cells to MESH1 was derived by zero transformation, followed by the effects of TAZ restoration to define the contribution of TAZ repression to the transcriptome features of human stringent response. The transcriptome data will be useful for the mechanistic understanding of the functional role of MESH1 in human cancer cells.
| S-EPMC9905932 | biostudies-literature