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Title:
Enhancer–promoter interactions are encoded by complex genomic signatures on looping chromatin | Nature Genetics
Description:
Sean Whalen and colleagues present a computational method, TargetFinder, for reconstructing three-dimensional regulatory landscapes using one-dimensional genomic features. TargetFinder identifies the minimal set of features necessary to predict individual interacting enhancer–promoter pairs and accurately distinguishes them from non-interacting pairs. Discriminating the gene target of a distal regulatory element from other nearby transcribed genes is a challenging problem with the potential to illuminate the causal underpinnings of complex diseases. We present TargetFinder, a computational method that reconstructs regulatory landscapes from diverse features along the genome. The resulting models accurately predict individual enhancer–promoter interactions across multiple cell lines with a false discovery rate up to 15 times smaller than that obtained using the closest gene. By evaluating the genomic features driving this accuracy, we uncover interactions between structural proteins, transcription factors, epigenetic modifications, and transcription that together distinguish interacting from non-interacting enhancer–promoter pairs. Most of this signature is not proximal to the enhancers and promoters but instead decorates the looping DNA. We conclude that complex but consistent combinations of marks on the one-dimensional genome encode the three-dimensional structure of fine-scale regulatory interactions.
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nature portfolio author information authors permissions reprints privacy policy ccaat/enhancer-binding protein β advertising long-range interaction landscape lncrna–protein interaction prediction microarray gene-expression data long-range interacting elements leveraging enhancer-promoter interactions social media interacting enhancer–promoter pairs fine-scale regulatory interactions enhancer–promoter interactions cell-type-specific variants fast gapped-read alignment automating chromatin-state discovery supplementary figures 1–20 high-resolution capture authors correspondence springerlink instant access high-resolution map nature 478 nature 489 nature 459 nature 473 nature 512 nature 462 nature 518 nature 504 nature 469 nature 457 nature 431 nature 460 nature nf-κb-dependent regulation genome-scale functional characterization distant enhancer function 3d genome connecting temporal gene expression linking disease associations secure chromatin interactions model-based analysis ctcf insulator protein human genetics regulatory information core promoter factor data analysis promoter-proximal pausing
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headline:Enhancerâpromoter interactions are encoded by complex genomic signatures on looping chromatin
description:Sean Whalen and colleagues present a computational method, TargetFinder, for reconstructing three-dimensional regulatory landscapes using one-dimensional genomic features. TargetFinder identifies the minimal set of features necessary to predict individual interacting enhancerâpromoter pairs and accurately distinguishes them from non-interacting pairs. Discriminating the gene target of a distal regulatory element from other nearby transcribed genes is a challenging problem with the potential to illuminate the causal underpinnings of complex diseases. We present TargetFinder, a computational method that reconstructs regulatory landscapes from diverse features along the genome. The resulting models accurately predict individual enhancerâpromoter interactions across multiple cell lines with a false discovery rate up to 15 times smaller than that obtained using the closest gene. By evaluating the genomic features driving this accuracy, we uncover interactions between structural proteins, transcription factors, epigenetic modifications, and transcription that together distinguish interacting from non-interacting enhancerâpromoter pairs. Most of this signature is not proximal to the enhancers and promoters but instead decorates the looping DNA. We conclude that complex but consistent combinations of marks on the one-dimensional genome encode the three-dimensional structure of fine-scale regulatory interactions.
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Gene regulation
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description:Sean Whalen and colleagues present a computational method, TargetFinder, for reconstructing three-dimensional regulatory landscapes using one-dimensional genomic features. TargetFinder identifies the minimal set of features necessary to predict individual interacting enhancerâpromoter pairs and accurately distinguishes them from non-interacting pairs. Discriminating the gene target of a distal regulatory element from other nearby transcribed genes is a challenging problem with the potential to illuminate the causal underpinnings of complex diseases. We present TargetFinder, a computational method that reconstructs regulatory landscapes from diverse features along the genome. The resulting models accurately predict individual enhancerâpromoter interactions across multiple cell lines with a false discovery rate up to 15 times smaller than that obtained using the closest gene. By evaluating the genomic features driving this accuracy, we uncover interactions between structural proteins, transcription factors, epigenetic modifications, and transcription that together distinguish interacting from non-interacting enhancerâpromoter pairs. Most of this signature is not proximal to the enhancers and promoters but instead decorates the looping DNA. We conclude that complex but consistent combinations of marks on the one-dimensional genome encode the three-dimensional structure of fine-scale regulatory interactions.
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