ArticleProceedings of the National Academy of Sciences of the United States of America2009
Genome-wide discovery of functional transcription factor binding sites by comparative genomics: the case of Stat3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- A pre-trained large generative model for translating single-cell transcriptomes to proteomes.Nature biomedical engineering · 2026Article
- Out of Nucleus: Serine 727 Phosphorylation Orchestrates Non-Canonical STAT3 Functions-Relevance to Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Review
- Article
- Pathobiont-driven antibody sialylation through IL-10 undermines vaccination.The Journal of clinical investigation · 2024Article
- Prmt7 regulates the JAK/STAT/Socs3 signaling pathway in postmenopausal cardiomyopathy.Experimental & molecular medicine · 2024Article
- MAE-seq refines regulatory elements across the genome.Nucleic acids research · 2024Article
- ETV7 reduces inflammatory responses in breast cancer cells by repressing the TNFR1/NF-κB axis.Cell death & disease · 2023Article
- β-Klotho promotes glycolysis and glucose-stimulated insulin secretion via GP130.Nature metabolism · 2022Article
- STAT3 induces breast cancer growth via ANGPTL4, MMP13 and STC1 secretion by cancer associated fibroblasts.Oncogene · 2022Article
- Review
- Germline STAT3 gain-of-function mutations in primary immunodeficiency: Impact on the cellular and clinical phenotype.Biomedical journal · 2021Review
- High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Elevated Phosphorylated STAT3.Frontiers in immunology · 2021Article
- Stat3 oxidation-dependent regulation of gene expression impacts on developmental processes and involves cooperation with Hif-1α.PloS one · 2020Article
- UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis.Oncogenesis · 2019Article
- NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis-related genes expression.Cellular and molecular life sciences : CMLS · 2019Article
- Preconditioned adipose-derived stem cells ameliorate cardiac fibrosis by regulating macrophage polarization in infarcted rat hearts through the PI3K/STAT3 pathway.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- CD28 Individual Signaling Up-regulates Human IL-17A Expression by Promoting the Recruitment of RelA/NF-κB and STAT3 Transcription Factors on the Proximal Promoter.Frontiers in immunology · 2019Article
- STAT3 enhances the constitutive activity of AGC kinases in melanoma by transactivating PDK1.Cell & bioscience · 2019Article
- Nucleus, Mitochondrion, or Reticulum? STAT3 à La Carte.International journal of molecular sciences · 2018Review
- STAT3 in Skeletal Muscle Function and Disorders.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The identification of direct targets of transcription factors is a key problem in the study of gene regulatory networks. However, the use of high throughput experimental methods, such as ChIP-chip and ChIP-sequencing, is limited by their high cost and strong dependence on cellular type and context. We developed a computational method for the genome-wide identification of functional transcription factor binding sites based on positional weight matrices, comparative genomics, and gene expression profiling. The method was applied to Stat3, a transcription factor playing crucial roles in inflammation, immunity and oncogenesis, and able to induce distinct subsets of target genes in different cell types or conditions. A newly generated positional weight matrix enabled us to assign affinity scores of high specificity, as measured by EMSA competition assays. Phylogenetic conservation with 7 vertebrate species was used to select the binding sites most likely to be functional. Validation was carried out on predicted sites within genes identified as differentially expressed in the presence or absence of Stat3 by microarray analysis. Twelve of the fourteen sites tested were bound by Stat3 in vivo, as assessed by Chromatin Immunoprecipitation, allowing us to identify 9 Stat3 transcriptional targets. Given its high validation rate, and the availability of large transcription factor-dependent gene expression datasets obtained under diverse experimental conditions, our approach appears to be a valid alternative to high-throughput experimental assays for the discovery of novel direct targets of transcription factors.
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