ArticleMolecular systems biology2010
Identifying the genetic determinants of transcription factor activity.
Article in Molecular systems biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Kar4 acts as a Ste12 regulator inbioRxiv : the preprint server for biology · 2025Article
- Gene regulatory networks in disease and ageing.Nature reviews. Nephrology · 2024Review
- Identifying genetic regulatory variants that affect transcription factor activity.Cell genomics · 2023Article
- Inferring TF activities and activity regulators from gene expression data with constraints from TF perturbation data.Bioinformatics (Oxford, England) · 2021Article
- Molecular and evolutionary processes generating variation in gene expression.Nature reviews. Genetics · 2021Review
- Identification of novel cerebellar developmental transcriptional regulators with motif activity analysis.BMC genomics · 2019Article
- Genetics ofeLife · 2018Article
- Identification of putative regulatory regions and transcription factors associated with intramuscular fat content traits.BMC genomics · 2018Article
- Article
- Conservation, evolution, and regulation of splicing during prefrontal cortex development in humans, chimpanzees, and macaques.RNA (New York, N.Y.) · 2018Article
- Treatment-associatedOncotarget · 2018Article
- A functional strategy to characterize expression Quantitative Trait Loci.Human genetics · 2017Article
- Network-based approaches that exploit inferred transcription factor activity to analyze the impact of genetic variation on gene expression.Current opinion in systems biology · 2017Article
- Identifying genetic modulators of the connectivity between transcription factors and their transcriptional targets.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The role of regulatory variation in complex traits and disease.Nature reviews. Genetics · 2015Review
- Harnessing natural sequence variation to dissect posttranscriptional regulatory networks in yeast.G3 (Bethesda, Md.) · 2014Article
- Mapping yeast transcriptional networks.Genetics · 2013Review
- Linking proteomic and transcriptional data through the interactome and epigenome reveals a map of oncogene-induced signaling.PLoS computational biology · 2013Article
- One Hand Clapping: detection of condition-specific transcription factor interactions from genome-wide gene activity data.Nucleic acids research · 2012Article
- Perturbation-based analysis and modeling of combinatorial regulation in the yeast sulfur assimilation pathway.Molecular biology of the cell · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Analysis of parallel genotyping and expression profiling data has shown that mRNA expression levels are highly heritable. Currently, only a tiny fraction of this genetic variance can be mechanistically accounted for. The influence of trans-acting polymorphisms on gene expression traits is often mediated by transcription factors (TFs). We present a method that exploits prior knowledge about the in vitro DNA-binding specificity of a TF in order to map the loci ('aQTLs') whose inheritance modulates its protein-level regulatory activity. Genome-wide regression of differential mRNA expression on predicted promoter affinity is used to estimate segregant-specific TF activity, which is subsequently mapped as a quantitative phenotype. In budding yeast, our method identifies six times as many locus-TF associations and more than twice as many trans-acting loci as all existing methods combined. Application to mouse data from an F2 intercross identified an aQTL on chromosome VII modulating the activity of Zscan4 in liver cells. Our method has greatly improved statistical power over existing methods, is mechanism based, strictly causal, computationally efficient, and generally applicable.
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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.