ArticleGenome research2010
Genome-wide discovery of human heart enhancers.
Article in Genome research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
89 citing papers in PubMed, 128 citations in OpenAlex.
- Procollagen IIA mediates positive feedback control of the mouse cardiogenic transcriptional network.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The combinatorial binding syntax of transcription factors in forebrain-specific enhancers.Biology open · 2025Article
- Cell-type-directed design of synthetic enhancers.Nature · 2024Article
- Cardiac Transcription Factors and Regulatory Networks.Advances in experimental medicine and biology · 2024Review
- RefSeq Functional Elements as experimentally assayed nongenic reference standards and functional interactions in human and mouse.Genome research · 2022Article
- Genomic enhancers in cardiac development and disease.Nature reviews. Cardiology · 2022Review
- Fish-Ing for Enhancers in the Heart.International journal of molecular sciences · 2021Review
- SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models.BMC research notes · 2021Article
- Heart Enhancers: Development and Disease Control at a Distance.Frontiers in genetics · 2021Review
- Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.Developmental biology · 2020Article
- Supervised enhancer prediction with epigenetic pattern recognition and targeted validation.Nature methods · 2020Article
- Epigenetic and Transcriptional Networks Underlying Atrial Fibrillation.Circulation research · 2020Review
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
- Identification of human silencers by correlating cross-tissue epigenetic profiles and gene expression.Genome research · 2019Article
- The function of miR-143, miR-145 and the MiR-143 host gene in cardiovascular development and disease.Vascular pharmacology · 2019Review
- Transcriptional Programs and Regeneration Enhancers Underlying Heart Regeneration.Journal of cardiovascular development and disease · 2018Review
- Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development.Nature communications · 2018Article
- Human cardiacGenome research · 2018Article
- Exploiting genetic variation to uncover rules of transcription factor binding and chromatin accessibility.Nature communications · 2018Article
- A new method for enhancer prediction based on deep belief network.BMC bioinformatics · 2017Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The various organogenic programs deployed during embryonic development rely on the precise expression of a multitude of genes in time and space. Identifying the cis-regulatory elements responsible for this tightly orchestrated regulation of gene expression is an essential step in understanding the genetic pathways involved in development. We describe a strategy to systematically identify tissue-specific cis-regulatory elements that share combinations of sequence motifs. Using heart development as an experimental framework, we employed a combination of Gibbs sampling and linear regression to build a classifier that identifies heart enhancers based on the presence and/or absence of various sequence features, including known and putative transcription factor (TF) binding specificities. In distinguishing heart enhancers from a large pool of random noncoding sequences, the performance of our classifier is vastly superior to four commonly used methods, with an accuracy reaching 92% in cross-validation. Furthermore, most of the binding specificities learned by our method resemble the specificities of TFs widely recognized as key players in heart development and differentiation, such as SRF, MEF2, ETS1, SMAD, and GATA. Using our classifier as a predictor, a genome-wide scan identified over 40,000 novel human heart enhancers. Although the classifier used no gene expression information, these novel enhancers are strongly associated with genes expressed in the heart. Finally, in vivo tests of our predictions in mouse and zebrafish achieved a validation rate of 62%, significantly higher than what is expected by chance. These results support the existence of underlying cis-regulatory codes dictating tissue-specific transcription in mammalian genomes and validate our enhancer classifier strategy as a method to uncover these regulatory codes.
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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.