ArticleNature2012
An expansive human regulatory lexicon encoded in transcription factor footprints.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 487 papers.
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Who cites it
487 citing papers in PubMed.
- Article
- Interplay between circadian and other transcription factors-Implications for cycling transcriptome reprogramming.FEBS letters · 2026Review
- Identification of novel DNA sequence motifs that modulate transcription in T cells.BMC genomics · 2026Article
- Intrinsically disordered regions facilitate target search to drive promoter selectivity by a yeast transcription factor.Nature communications · 2025Article
- Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq.Protein & cell · 2025Article
- HBMC bioinformatics · 2025Article
- Coordinated regulation by lncRNAs results in tight lncRNA-target couplings.Cell genomics · 2025Article
- Decoding the Effects of Bexarotene treatment on brain of AD-like model mice: Single-Cell Transcriptomics and Chromatin Accessibility Analysis.Research square · 2025Article
- Transcriptional regulation as a dose-dependent process: insights from transcription factor tuning.Open biology · 2025Review
- A haplotype-resolved view of human gene regulation.bioRxiv : the preprint server for biology · 2025Article
- Spatial epigenomic niches underlie glioblastoma cell state plasticity.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic Plasticity Drives Carcinogenesis and Multi-Therapy Resistance in Multiple Myeloma.Research square · 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
- p53motifDB: integration of genomic information and tumour suppressor p53 binding motifs.Database : the journal of biological databases and curation · 2025Article
- ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants.bioRxiv : the preprint server for biology · 2025Article
- Transcription Factor-Wide Association Studies to Identify Functional SNPs in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- BPDCN MYB fusions regulate cell cycle genes, impair differentiation, and induce myeloid-dendritic cell leukemia.JCI insight · 2024Article
- Single chromatin fiber profiling and nucleosome position mapping in the human brain.Cell reports methods · 2024Article
- A novel interpretable deep learning-based computational framework designed synthetic enhancers with broad cross-species activity.Nucleic acids research · 2024Article
427 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors.
Funding
Abstract
Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.
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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.