Distal enhancers loop to proximal enhancers, not to promoters
Author:
- 26 August 2025
- journal article
- editorial
- Published by Springer Nature in Nature Reviews Molecular Cell Biology
- Vol. 26 (10) , 730-731
Abstract
Although enhancers activate transcription from long distances, they stimulate transcription only through short-range interactions with the RNA polymerase II machinery. I posit that action at a distance is mediated by loops between distal and proximal enhancers that thereby bring proteins associated with distal enhancers near promoters. This Comment posits that enhancers stimulate the transcription machinery only through short-range interactions and, therefore, that enhancer activity at a distance is mediated by chromatin loops between distal and proximal enhancers, not between enhancers and promoters.Keywords
This publication has 15 references indexed in Scilit:
- LDB1 establishes multi-enhancer networks to regulate gene expressionMolecular Cell, 2024
- Enhancer cooperativity can compensate for loss of activity over large genomic distancesMolecular Cell, 2024
- Long-range regulation of transcription scales with genomic distance in a gene-specific mannerMolecular Cell, 2024
- FOXP3 recognizes microsatellites and bridges DNA through multimerizationNature, 2023
- The Mediator complex regulates enhancer-promoter interactionsNature Structural & Molecular Biology, 2023
- GAGA-associated factor fosters loop formation in the Drosophila genomeMolecular Cell, 2023
- The Mediator complex as a master regulator of transcription by RNA polymerase IINature Reviews Molecular Cell Biology, 2022
- Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancersNature Genetics, 2014
- Controlling Long-Range Genomic Interactions at a Native Locus by Targeted Tethering of a Looping FactorCell, 2012
- Ordered Recruitment of Transcription and Chromatin Remodeling Factors to a Cell Cycle– and Developmentally Regulated PromoterCell, 1999