Hmt1p is the predominant arginine methyltransferase in Saccharomyces cerevisiae. Its substrate proteins are involved in transcription, transcriptional regulation, nucleocytoplasmic transport and RNA splicing. Functionally, Hmt1p-catalysed methylation can also modulate protein-protein interactions. Despite Hmt1p being well-characterised, the effects of its knockout on the proteome and transcriptome have not been reported. SILAC-based analyses of the hmt1 proteome, in mid-log exponential growth, revealed a decreased abundance of phosphate-associated proteins including Pho84p (phosphate transporter), Pho8p (vacuolar alkaline phosphatase), Pho3p (acid phosphatase) along with Vtc1p, Vtc3p and Vtc4p (subunits of the vacuolar transporter chaperone complex). RNA-Seq and microarray analysis revealed a downregulation of phosphate-responsive genes in hmt1, including PHO5, PHO11 and PHO12 (acid phosphatases), PHO84 and PHO89 (phosphate transporters) and VTC3 (vacuolar transporter chaperone). Consistent with these observations, we observed a dysregulation of phosphate homeostasis in hmt1, with a general decrease in extracellular phosphatase production and a decrease in total Pi in phosphate replete medium. We show that the transcription factor Pho4p, responsible for activation of the PHO pathway, can be methylated by Hmt1p at Arg-241 and is the likely cause of phosphate dysregulation in hmt1. However, the methylation of Pho4p does not affect its nucleocytoplasmic localisation. We propose that the methylation of Pho4p may affect either its capacity to multimerise, its capacity to interact with Pho2p or target DNA, or may affect Pho4p phosphorylation at Ser-242 and/or Ser 243. Our study highlights a previously unknown function of Hmt1p in the regulation of phosphate homeostasis and suggests a means by which sensing of AdoMet may affect intracellular phosphate concentration.
Knockout of the Hmt1p Arginine Methyltransferase in <i>Saccharomyces cerevisiae</i> Leads to the Dysregulation of Phosphate-associated Genes and Processes.
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View SamplesDevelopment of the female tract results from the carefull coordination of numerous signaling pathways. Here, we evaluated the role of hippo pathway in the development of the female reproductive tract.
<i>Lats1</i> and <i>Lats2</i> are required for the maintenance of multipotency in the Müllerian duct mesenchyme.
Specimen part
View SamplesThis work is part of the paper: Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model, Rothweiler S et al, Laboratory Investigation, 2014
Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model.
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View SamplesRNA-seq was performed using the RNA extracted from the bottom half of right lobe of mouse livers. Mice fall into two groups, mutant group which express ectopic hURI and their control littermates which do not express hURI. Two time points were considered in the study, 1-week-old mice, expressing hURI since 1 week (n =3, 4 for control and mutant, respectively) and 8-week-old mice expressing hURI since 8 week (n= 4, 3 for control and mutant, respectively), as hURI is expressed since conception. Overall design: Determination of differentially expressed transcripts over two time points (1 week and 8 weeks) in mouse livers expressing hURI (1 week and 8 weeks).
Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sex, Age, Specimen part
View SamplesWe show that an excess of VEGF-B protects the heart via adaptive cardiac hypertrophy and increased coronary arterial reserve, and by inducing a shift from lipid to glucose metabolism.
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
Sex, Age, Specimen part
View SamplesLymphatic valves are specialized units regularly distributed along collecting vessels that allow unidirectional forward propulsion of the lymph, and its efficient transport from tissues to the bloodstream. Lymphatic endothelial cells that cover lymphatic valve sinuses are subjected to complex flow patterns, due to recirculation of the lymph during the collecting vessel pumping cycle. They also express high levels of FOXC2 transcription factor.
FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.
Specimen part, Treatment
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