ArticleMolecular systems biology2009
Dissection of a complex transcriptional response using genome-wide transcriptional modelling.
Article in Molecular systems biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Kinetic modeling of stem cell transcriptome dynamics to identify regulatory modules of normal and disturbed neuroectodermal differentiation.Nucleic acids research · 2020Article
- Global Analysis of the Human RNA Degradome Reveals Widespread Decapped and Endonucleolytic Cleaved Transcripts.International journal of molecular sciences · 2020Article
- Gene Expression in Parp1 Deficient Mice Exposed to a Median Lethal Dose of Gamma Rays.Radiation research · 2018Article
- Article
- A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.Oncotarget · 2015Article
- Contributions of transcription and mRNA decay to gene expression dynamics of fission yeast in response to oxidative stress.RNA biology · 2014Article
- Genome-wide technology for determining RNA stability in mammalian cells: historical perspective and recent advantages based on modified nucleotide labeling.RNA biology · 2012Review
- Computational inference of mRNA stability from histone modification and transcriptome profiles.Nucleic acids research · 2012Article
- Identifying targets of multiple co-regulating transcription factors from expression time-series by Bayesian model comparison.BMC systems biology · 2012Article
- Hierarchical modularity in ERα transcriptional network is associated with distinct functions and implicates clinical outcomes.Scientific reports · 2012Article
- Coupled pre-mRNA and mRNA dynamics unveil operational strategies underlying transcriptional responses to stimuli.Molecular systems biology · 2011Article
- Crosstalk between c-Jun and TAp73alpha/beta contributes to the apoptosis-survival balance.Nucleic acids research · 2011Article
- Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells.Nature biotechnology · 2011Article
- Virtual mutagenesis of the yeast cyclins genetic network reveals complex dynamics of transcriptional control networks.PloS one · 2011Article
- Weighted correlation network analysis (WGCNA) applied to the tomato fruit metabolome.PloS one · 2011Article
- Global coordination of transcriptional control and mRNA decay during cellular differentiation.Molecular systems biology · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Modern genomics technologies generate huge data sets creating a demand for systems level, experimentally verified, analysis techniques. We examined the transcriptional response to DNA damage in a human T cell line (MOLT4) using microarrays. By measuring both mRNA accumulation and degradation over a short time course, we were able to construct a mechanistic model of the transcriptional response. The model predicted three dominant transcriptional activity profiles-an early response controlled by NFkappaB and c-Jun, a delayed response controlled by p53, and a late response related to cell cycle re-entry. The method also identified, with defined confidence limits, the transcriptional targets associated with each activity. Experimental inhibition of NFkappaB, c-Jun and p53 confirmed that target predictions were accurate. Model predictions directly explained 70% of the 200 most significantly upregulated genes in the DNA-damage response. Genome-wide transcriptional modelling (GWTM) requires no prior knowledge of either transcription factors or their targets. GWTM is an economical and effective method for identifying the main transcriptional activators in a complex response and confidently predicting their targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.