ArticleNature genetics2023
Precise modulation of transcription factor levels identifies features underlying dosage sensitivity.
Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 130 citations in OpenAlex.
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- Dose-dependent sensitivity of human three-dimensional chromatin to a heart disease-linked transcription factor.Science (New York, N.Y.) · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- Buffering of gene dosage response curves for human complex traits.Cell genomics · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Elevated MyoD1 levels expand genome-wide binding and the repertoire of regulated genes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dose-dependent hormone actions at estrogen receptor enhancers specify distinct molecular and biological outcomes.Science advances · 2026Article
- Unveiling a novel role for p19Arf (alternative reading frame) in mESC differentiation toward the pancreatic lineage.Scientific reports · 2026Article
- Continuous negative autoregulation fine-tunes dosage-sensitive transcription factor expression to maintain post-mitotic neuron identity.bioRxiv : the preprint server for biology · 2026Article
- Functional impact of genetic background on variable expressivity in neurodevelopmental disorders.Nature communications · 2026Article
- Dual role of ZIC2 during neural induction: from priming transcription factor to enhancer activator.Nucleic acids research · 2026Article
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- Enhancer hubs govern chromatin topology and Th17 cell identity.bioRxiv : the preprint server for biology · 2026Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 8 institutions in 4 countries.
Funding
Abstract
Transcriptional regulation exhibits extensive robustness, but human genetics indicates sensitivity to transcription factor (TF) dosage. Reconciling such observations requires quantitative studies of TF dosage effects at trait-relevant ranges, largely lacking so far. TFs play central roles in both normal-range and disease-associated variation in craniofacial morphology; we therefore developed an approach to precisely modulate TF levels in human facial progenitor cells and applied it to SOX9, a TF associated with craniofacial variation and disease (Pierre Robin sequence (PRS)). Most SOX9-dependent regulatory elements (REs) are buffered against small decreases in SOX9 dosage, but REs directly and primarily regulated by SOX9 show heightened sensitivity to SOX9 dosage; these RE responses partially predict gene expression responses. Sensitive REs and genes preferentially affect functional chondrogenesis and PRS-like craniofacial shape variation. We propose that such REs and genes underlie the sensitivity of specific phenotypes to TF dosage, while buffering of other genes leads to robust, nonlinear dosage-to-phenotype relationships.
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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.