ArticleGenome research2015
Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/ enhancer-binding protein beta binding sites.
Article in Genome research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Atlas of nascent RNA transcripts reveals tissue-specific enhancer to gene linkages.BMC genomics · 2025Article
- Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.Nature communications · 2024Article
- Multinomial Convolutions for Joint Modeling of Regulatory Motifs and Sequence Activity Readouts.Genes · 2022Article
- Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use.International journal of molecular sciences · 2022Review
- Shared Transcriptional Machinery at Homologous Alleles Leads to Reduced Transcription in EarlyFrontiers in cell and developmental biology · 2022Article
- Molecular competition can shape enhancer activity in theiScience · 2021Article
- Search and comparison of (epi)genomic feature patterns in multiple genome browser tracks.BMC bioinformatics · 2020Article
- Distinct Roles for BET Family Members in Estrogen Receptor α Enhancer Function and Gene Regulation in Breast Cancer Cells.Molecular cancer research : MCR · 2019Article
- Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming.Nature communications · 2019Article
- Shared nucleotide flanks confer transcriptional competency to bZip core motifs.Nucleic acids research · 2018Article
- Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines.Journal of visualized experiments : JoVE · 2018Article
- A genome-wide interactome of DNA-associated proteins in the human liver.Genome research · 2017Article
- Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.Cell systems · 2017Article
- DNA Sequence Constraints Define Functionally Active Steroid Nuclear Receptor Binding Sites in Chromatin.Endocrinology · 2017Article
- Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2017Article
- A systematic comparison reveals substantial differences in chromosomal versus episomal encoding of enhancer activity.Genome research · 2017Article
- Computational Approaches for Mining GRO-Seq Data to Identify and Characterize Active Enhancers.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Decoding transcriptional enhancers: Evolving from annotation to functional interpretation.Seminars in cell & developmental biology · 2016Review
- Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.Genome medicine · 2016Article
- Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity.Genome biology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Transcription factors (TFs) bind to thousands of DNA sequences in mammalian genomes, but most of these binding events appear to have no direct effect on gene expression. It is unclear why only a subset of TF bound sites are actively involved in transcriptional regulation. Moreover, the key genomic features that accurately discriminate between active and inactive TF binding events remain ambiguous. Recent studies have identified promoter-distal RNA polymerase II (RNAP2) binding at enhancer elements, suggesting that these interactions may serve as a marker for active regulatory sequences. Despite these correlative analyses, a thorough functional validation of these genomic co-occupancies is still lacking. To characterize the gene regulatory activity of DNA sequences underlying promoter-distal TF binding events that co-occur with RNAP2 and TF sites devoid of RNAP2 occupancy using a functional reporter assay, we performed cis-regulatory element sequencing (CRE-seq). We tested more than 1000 promoter-distal CCAAT/enhancer-binding protein beta (CEBPB)-bound sites in HepG2 and K562 cells, and found that CEBPB-bound sites co-occurring with RNAP2 were more likely to exhibit enhancer activity. CEBPB-bound sites further maintained substantial cell-type specificity, indicating that local DNA sequence can accurately convey cell-type-specific regulatory information. By comparing our CRE-seq results to a comprehensive set of genome annotations, we identified a variety of genomic features that are strong predictors of regulatory element activity and cell-type-specific activity. Collectively, our functional assay results indicate that RNAP2 occupancy can be used as a key genomic marker that can distinguish active from inactive TF bound sites.
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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.