Investigating genes regulated by Nrg1 nuclear back signaling.
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ABSTRACT:
PROVIDER: PRJNA1119194 | ENA |
REPOSITORIES: ENA
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Project description:Nrg1 proteins can be cleaved by gamma secretase in the synaptic membrane. Following cleavage the c-terminal domain of Nrg1 translocates to the nucleus. Which genes are regulated by this signaling is unclear. Here we investigated which genes are regulated.
2024-10-17 | GSE268856 | GEO
Project description:Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, We used DNA-protein pull-down using Nrg1 enhancer sequence as bait followed by LC/MS and identified RBPJ as a key component of the Nrg1 enhanceosome. We show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where RBPJ, P300, and SETD1A are recruited to upregulate Nrg1 expression.
2023-01-29 | PXD038668 | Pride
Project description:The Cryptococcus neoformans NRG1 gene was identified using gene microarrays to define putative transcription factor genes regulated by the cyclic AMP (cAMP) signal transduction pathway. Disruption of NRG1 results in delayed capsule formation and mating, two phenotypes that are directly controlled by cAMP signaling. Putative targets of the Nrg1 transcription factor were identified using a second genome microarray to define differences in the transcriptomes of the wild-type and nrg1 mutant strains. These experiments implicate Nrg1 in the transcriptional control of multiple genes involved in carbohydrate metabolism and substrate oxidation, as well as the UGD1 gene encoding a UDP-glucose dehydrogenase required for polysaccharide capsule production and cell wall integrity. In addition to being under transcriptional control of the cAMP pathway, Nrg1 contains a putative protein kinase A phosphorylation site; mutation of this motif results in reduced Nrg1 activity. Consistent with prior studies in hypocapsular mutants, the nrg1 mutant strain is attenuated in an animal model of disseminated cryptococcal disease.
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Project description:Transcriptome prolifing analysis was performed in 22Pc-EP cells to identify differentially regulated genes by enzalutamide and NRG1
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Project description:Schizophrenia is a complex genetic neurodevelopmental disorder. eQTLs form bulk of the genetic variation contributing to schizophrenia. However, there is no known mechanism explaining regulation of expression of eQTL associated risk genes and underlying neurodevelopmental processes that are part of the cellular pathology. Neuregulin1-ErbB4 signaling plays a crucial role in synaptogenesis and has been implicated in schizophrenia. Gamma secretase mediated NRG1 nuclear back-signaling is thought to be involved in transcriptional regulation. A psychosis-associated missense mutation in NRG1 (rs74942016) has been predicted to impair nuclear back-signaling thereby implicating this mode of signaling in the underlying cellular pathology.
2023-12-31 | GSE192869 | GEO
Project description:Neuregulin (NRG) signaling through the receptor tyrosine kinase, ERBB3, is required for embryonic development, and dysregulated signaling has been associated with cancer progression. Here, we show that NRG1/ERBB3 signaling inhibits melanocyte (MC) maturation and promotes undifferentiated, migratory and proliferative cellular characteristics. Embryonic analyses demonstrated that initial MC specification and distribution were not dependent on ERBB3 signaling. However NRG1/ERBB3 signaling was both necessary and sufficient to inhibit differentiation of later stages of MC development in culture. Analysis of tissue arrays of human melanoma samples suggests that ERBB3 signaling may also contribute to metastatic progression of melanoma as ERBB3 was phosphorylated in primary tumors compared with nevi or metastatic lesions. Neuregulin 1-treated MCs demonstrated increased proliferation and invasion and altered morphology concomitant with decreased levels of differentiation genes, increased levels of proliferation genes and altered levels of melanoma progression and metastases genes. ERBB3 activation in primary melanomas suggests that NRG1/ERBB3 signaling may contribute to the progression of melanoma from benign nevi to malignancies. We propose that targeting ERBB3 activation and downstream genes identified in this study may provide novel therapeutic interventions for malignant melanoma. Gene expression changes are compared between Melan-Ink4a cells stimulated with NRG1-b1 (NRG1) for 21 days and NRG1 untreated Melan-INK4a cells in triplicate using Affymetrix Mouse GeneChip 1.0 ST chip .
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Project description:Discovery of NRG1 isoforms
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Project description:In DRG neurons NRG1 type III intacellular domain (ICD) moves to the nucleus upon contact with Schwann cells. We aimed to investigate genes up/down regulated by ICD.
2014-09-26 | GSE61784 | GEO
Project description:Hyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, We used DNA-protein pull-down using Nrg1 enhancer sequence as bait followed by LC/MS and identified RBPJ as a key component of the Nrg1 enhanceosome. We show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where RBPJ, P300, and SETD1A are recruited to upregulate Nrg1 expression.
2022-12-21 | MSV000090951 | MassIVE
Project description:A homologue of the transcriptional repressor ScNrg1 described previously in the budding yeast and Candida albicans NRG1 wich plays an essential role in repressing hyphal development in both Saccharomyces cerevisiae and C. albicans, was found in Ustilago maydis. In S. cerevisiae it regulates a set of stress-responsive genes, also in Cryptococcus neoformans is involved in pathogenesis. In this work, we describe the effect of the absence of the U. maydis NRG1 gene in cell response to acid pH, mannosylerithritol lipids production, and cellular response to several stressful conditions. In U. maydis, NRG1 is required for filamentous growth and appears to be essential to respond to pH changes, and oxidative stress accurately. By comparing gene expression in a wild type strain versus nrg1 mutant strain of the fungus trough RNA_Seq analyses, it turned out to act as transcriptional factor altering the expression of 368 genes (205 up-regulated, 163 downregulated). Most relevant cellular processes affected by NRG1 are osmotic stress pathway, pH response, internal environmental sensor mechanism, represented by the genes Hog1, Rim101, and WCO1 respectively, also, all the genes present in the mannosylerithritol lipids production pathway, even under conditions not favorable for the production of glycolipids. Among previous specific functions described before for this transcriptional regulator as a glucose repressor, it seems to have an important role in metabolic adaptation, cellular transport, cell rescue defense and interaction with the environment.
2021-03-03 | GSE133840 | GEO