ArticleNature2014
Conservation of trans-acting circuitry during mammalian regulatory evolution.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 2 of them syntheses that pooled it.
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Who cites it
146 citing papers in PubMed, 2 syntheses or guidelines pooled it, 231 citations in OpenAlex.
- Conservation and divergence of the p53 gene regulatory network between mice and humans.Oncogene · 2019Pooled it
- The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.Nature genetics · 2016Pooled it
- Flexible use of conserved motifs constrains genome access in cell type evolution.Nature ecology & evolution · 2026Article
- Deep learning enabled prediction of nuclear lamina-associated chromatin.Patterns (New York, N.Y.) · 2026Article
- Cave adaptation drives coordinated transcriptional remodeling across diverse cell types in the brain of a teleost fish.bioRxiv : the preprint server for biology · 2026Article
- From time-course expression to gene regulation: direct linear ODE inference without finite-difference approximation.bioRxiv : the preprint server for biology · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Characterization of Transcriptional, Epigenetic, and Phenotypic Plasticity and Discovery of Biomarkers in Acute and Chronic Murine Schistosomiasis Infection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Widespread turnover of a conserved cis-regulatory code across 589 grass species.Molecular biology and evolution · 2026Article
- Inhibition of Phosphodiesterase 10A by MP-10 Rescues Behavioral Deficits and Normalizes Microglial Morphology and Synaptic Pruning in A Mouse Model of FOXP1 Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nidogen-1 suppresses cell proliferation, migration, and glycolysis via integrin β1-mediated HIF-1α downregulation in triple-negative breast cancer.Scientific reports · 2025Article
- Regulatory Plasticity of the Human Genome.Molecular biology and evolution · 2025Article
- A guide to studying 3D genome structure and dynamics in the kidney.Nature reviews. Nephrology · 2025Review
- KAS-ATAC reveals the genome-wide single-stranded accessible chromatin landscape of the human genome.Genome research · 2025Article
- Interspecies regulatory landscapes and elements revealed by novel joint systematic integration of human and mouse blood cell epigenomes.Genome research · 2024Article
- Inferring gene regulatory networks from single-cell transcriptomics based on graph embedding.Bioinformatics (Oxford, England) · 2024Article
- Implications of ZNF334 gene in lymph node metastasis of lung SCC: potential bypassing of cellular senescence.Journal of translational medicine · 2024Article
- Human gene regulatory evolution is driven by the divergence of regulatory element function in both cis and trans.Cell genomics · 2024Article
- Functional annotation of regulatory elements in rainbow trout uncovers roles of the epigenome in genetic selection and genome evolution.GigaScience · 2024Article
- SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks.Nature methods · 2023Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 2 institutions in 1 country.
Funding
Abstract
The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining ∼8.6 million transcription factor (TF) occupancy sites at nucleotide resolution. Here we show that mouse TF footprints conjointly encode a regulatory lexicon that is ∼95% similar with that derived from human TF footprints. However, only ∼20% of mouse TF footprints have human orthologues. Despite substantial turnover of the cis-regulatory landscape, nearly half of all pairwise regulatory interactions connecting mouse TF genes have been maintained in orthologous human cell types through evolutionary innovation of TF recognition sequences. Furthermore, the higher-level organization of mouse TF-to-TF connections into cellular network architectures is nearly identical with human. Our results indicate that evolutionary selection on mammalian gene regulation is targeted chiefly at the level of trans-regulatory circuitry, enabling and potentiating cis-regulatory plasticity.
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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.