Synthetic targeted optimization of plant promoters is becoming a part of progress in mainstream postgenomic agriculture along with hybridization of cultivated plants with wild congeners, as well as marker-assisted breeding. Therefore, here, for the first time, we compiled all the experimental data-on mutational effects in plant proximal promoters on gene expression-that we could find in PubMed. Some of these datasets cast doubt on both the existence and the uniqueness of the sought solution, which could unequivocally estimate effects of proximal promoter mutation on gene expression when plants are grown under various environmental conditions during their development. This means that the inverse problem under study is ill-posed. Furthermore, we found experimental data on in vitro interchangeability of plant and human TATA-binding proteins allowing the application of Tikhonov's regularization, making this problem well-posed. Within these frameworks, we created our Web service Plant_SNP_TATA_Z-tester and then determined the limits of its applicability using those data that cast doubt on both the existence and the uniqueness of the sought solution. We confirmed that the effects (of proximal promoter mutations on gene expression) predicted by Plant_SNP_TATA_Z-tester correlate statistically significantly with all the experimental data under study. Lastly, we exemplified an application of Plant_SNP_TATA_Z-tester to agriculturally valuable mutations in plant promoters.
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http://dx.doi.org/10.3390/ijms23158684 | DOI Listing |
Plant Methods
December 2024
School of Molecular Sciences, University of Western Australia, Crawley, WA, 6009, Australia.
The genus Flaveria has been studied extensively as a model for the evolution of C photosynthesis. Thus far, molecular analyses in this genus have been limited due to a dearth of genomic information and the lack of a rapid and efficient transformation protocol. Since their development, Agrobacterium-mediated transient transformation protocols have been instrumental in understanding many biological processes in a range of plant species.
View Article and Find Full Text PDFSci Rep
December 2024
Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, No. 55, Section 4, South People's Road, Chengdu, 610041, China.
MYD88 is an IL-6 primary response gene and, its upregulation of expression has been shown to be a poor prognostic factor in epithelial ovarian cancer (EOC). We investigated the effects of CpG methylation at the proximal promoter/5'UTR and IL-6/SP1/IRF1 signaling on upregulation of MYD88 and prognosis in EOC. We assessed CpG methylation at the proximal promoter/5'UTR of MYD88 using bisulfite sequencing/PCR in 103 EOC patients, 28 normal ovarian tissues and two EOC cell lines with differential expression of MYD88 and identified the impact of the level of CpG methylation on MYD88 upregulation by SP1/IRF1 with knockdown or blockade of IL-6.
View Article and Find Full Text PDFKidney Int
December 2024
Clinic of Internal Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Comprehensive Cancer Center Freiburg (CCCF), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner Site, Freiburg; Signalling Research Centres BIOSS and CIBSS, Faculty of Biology University of Freiburg, Freiburg, Germany. Electronic address:
RASSF1A is frequently biallelically inactivated in clear cell renal cell carcinoma (ccRCC) due to loss of chromosome 3p and promoter hypermethylation. Here we investigated the cellular and molecular consequences of single and combined deletion of the Rassf1a and Vhl tumor suppressor genes to model the common ccRCC genotype of combined loss of function of RASSF1A and VHL. In mouse embryonic fibroblasts and in primary kidney epithelial cells, double deletion of Rassf1a and Vhl caused chromosomal segregation defects and increased formation of micronuclei, demonstrating that pVHL and RASSF1A function to maintain genomic integrity.
View Article and Find Full Text PDFPLoS Genet
December 2024
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Background: The development and diversification of sensory proprioceptive neurons, which reside in the dorsal root ganglia (DRG) and express the tropomyosin receptor kinase C (TrkC), depend on the transcription factor (TF) Runx3. Runx3-deficient mice develop severe limb ataxia due to TrkC neuron cell death. Two additional TFs Pou4f1 (also called Brn3a) and Isl1 also play an important role in sensory neuron development.
View Article and Find Full Text PDFMol Cell
December 2024
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA. Electronic address:
Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc-finger transcription factor (TF) ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, how ZNF143/ZFP143 functions as a looping factor is not well understood.
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