ArticleEpigenetics & chromatin2015
Motif signatures in stretch enhancers are enriched for disease-associated genetic variants.
Article in Epigenetics & chromatin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Using a modular massively parallel reporter assay to discover context-dependent regulatory activity in type 2 diabetes-linked noncoding regions.HGG advances · 2026Article
- Donor-matched iPSC model reveals context-dependent T2D genetic signals in fibro-adipogenic progenitors.bioRxiv : the preprint server for biology · 2026Article
- Population-scale skeletal muscle single-nucleus multi-omic profiling reveals extensive context specific genetic regulation.bioRxiv : the preprint server for biology · 2024Article
- Endogenous retroviruses mediate transcriptional rewiring in response to oncogenic signaling in colorectal cancer.Science advances · 2024Article
- Super-Enhancers and Their Parts: From Prediction Efforts to Pathognomonic Status.International journal of molecular sciences · 2024Review
- Review
- A Transcription Start Site Map in Human Pancreatic Islets Reveals Functional Regulatory Signatures.Diabetes · 2021Article
- Missing heritability in Parkinson's disease: the emerging role of non-coding genetic variation.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- FactorNet: A deep learning framework for predicting cell type specific transcription factor binding from nucleotide-resolution sequential data.Methods (San Diego, Calif.) · 2019Article
- Super-enhancers: critical roles and therapeutic targets in hematologic malignancies.Journal of hematology & oncology · 2019Review
- Perturbing Enhancer Activity in Cancer Therapy.Cancers · 2019Review
- Cell Specificity of Human Regulatory Annotations and Their Genetic Effects on Gene Expression.Genetics · 2019Article
- Progressing super-enhancer landscape during mammary differentiation controls tissue-specific gene regulation.Nucleic acids research · 2018Article
- Super-enhancers are transcriptionally more active and cell type-specific than stretch enhancers.Epigenetics · 2018Article
- Expression of long non-coding RNAs in autoimmunity and linkage to enhancer function and autoimmune disease risk genetic variants.Journal of autoimmunity · 2017Article
- Article
- Genomics of Islet (Dys)function and Type 2 Diabetes.Trends in genetics : TIG · 2017Review
- Genetic regulatory signatures underlying islet gene expression and type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Parkinson's disease-associated genetic variation is linked to quantitative expression of inflammatory genes.PloS one · 2017Article
- DNA Hypomethylation in Intragenic and Intergenic Enhancer Chromatin of Muscle-Specific Genes Usually Correlates with their Expression.The Yale journal of biology and medicine · 2016Article
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Authors and funding
4 authors.
Funding
Abstract
backgroundStretch enhancers (SEs) are large chromatin-defined regulatory elements that are at least 3,000 base pairs (bps) long, in contrast to the median enhancer length of 800 bps. SEs tend to be cell-type specific, regulate cell-type specific gene expression, and are enriched in disease-associated genetic variants in disease-relevant cell types. Transcription factors (TFs) can bind to enhancers to modulate enhancer activity, and their sequence specificity can be represented by motifs. We hypothesize motifs can provide a biological context for how genetic variants contribute to disease.
resultsWe integrated chromatin state, gene expression, and chromatin accessibility [measured as DNase I Hypersensitive Sites (DHSs)] maps across nine different cell types. Motif enrichment analyses of chromatin-defined enhancer sequences identify several known cell-type specific "master" factors. Furthermore, de novo motif discovery not only recovers many of these motifs, but also identifies novel non-canonical motifs, providing additional insight into TF binding preferences. Across the length of SEs, motifs are most enriched in DHSs, though relative enrichment is also observed outside of DHSs. Interestingly, we show that single nucleotide polymorphisms associated with diseases or quantitative traits significantly overlap motif occurrences located in SEs, but outside of DHSs.
conclusionsThese results reinforce the role of SEs in influencing risk for diseases and suggest an expanded regulatory functional role for motifs that occur outside highly accessible chromatin. Furthermore, the motif signatures generated here expand our understanding of the binding preference of well-characterized TFs.
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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.