ArticleProceedings of the National Academy of Sciences of the United States of America2007
Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers.
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Who cites it
178 citing papers in PubMed, 315 citations in OpenAlex.
- Direct analysis of transcription factor protected cfDNA in plasma by ChIP-seq: measurement of altered CTCF binding in cancer is a novel biomarker for liquid biopsy.Clinical epigenetics · 2026Article
- EssTFNet: integration of adaptive time-frequency and DNA language models for interpretable human essential gene prediction.Briefings in bioinformatics · 2026Article
- An upstream secondary DNA motif within the IL3 insulator CTCF binding site is required for enhancer-blocking insulator activity.PloS one · 2026Article
- The Biological Function of Genome Organization.International journal of molecular sciences · 2025Review
- Dissecting the Emerging Regulatory and Mechanistic Paradigms of Transcribed Conserved Non-Coding Elements in Breast Cancer.Biomolecules · 2025Article
- Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.iScience · 2025Article
- Predicting CTCF cell type active binding sites in human genome.Scientific reports · 2024Article
- Understanding fundamental principles of enhancer biology at a model locus: Analysing the structure and function of an enhancer cluster at the α-globin locus.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Chromatin Organization and Transcriptional Programming of Breast Cancer Cell Identity.Endocrinology · 2023Review
- Article
- Auxin-inducible degron 2 system deciphers functions of CTCF domains in transcriptional regulation.Genome biology · 2023Article
- Role of primary aging hallmarks in Alzheimer´s disease.Theranostics · 2023Review
- A Tremendous Reorganization Journey for the 3D Chromatin Structure from Gametes to Embryos.Genes · 2022Review
- Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation.Nature communications · 2022Article
- Regulatory mechanisms ensuring coordinated expression of functionally related genes.Trends in genetics : TIG · 2022Review
- CTCF: an R/bioconductor data package of human and mouse CTCF binding sites.Bioinformatics advances · 2022Article
- Article
- Transcriptional enhancers and their communication with gene promoters.Cellular and molecular life sciences : CMLS · 2021Review
- The CCCTC-binding factor CTCF represses hepatitis B virus enhancer I and regulates viral transcription.Cellular microbiology · 2021Article
- ZNF143 mediates CTCF-bound promoter-enhancer loops required for murine hematopoietic stem and progenitor cell function.Nature communications · 2021Article
118 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, yet their function remains largely unknown. Experimental evidence suggests that many of these elements play regulatory roles, but little is known about regulatory motifs contained within them. Here we describe a systematic approach to discover and characterize regulatory motifs within mammalian CNEs by searching for long motifs (12-22 nt) with significant enrichment in CNEs and studying their biochemical and genomic properties. Our analysis identifies 233 long motifs (LMs), matching a total of approximately 60,000 conserved instances across the human genome. These motifs include 16 previously known regulatory elements, such as the histone 3'-UTR motif and the neuron-restrictive silencer element, as well as striking examples of novel functional elements. The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode. We show that it is bound by the RFX1 protein and identify thousands of conserved motif instances, suggesting a broad role for the RFX family in gene regulation. A second group of motifs (LM2*) does not match any previously known motif. We demonstrate by biochemical and computational methods that it defines a binding site for the CTCF protein, which is involved in insulator function to limit the spread of gene activation. We identify nearly 15,000 conserved sites that likely serve as insulators, and we show that nearby genes separated by predicted CTCF sites show markedly reduced correlation in gene expression. These sites may thus partition the human genome into domains of expression.
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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.