Project description:Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.
Project description:Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.
Project description:Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.
Project description:Chromosome structure in mammals is thought to regulate transcription by modulating spatial proximity between enhancers and promoters. However, the mechanisms by which this occurs remain elusive, and reports suggested moderate to no correlation between physical proximity and transcription. Whether and how chromosome structure is actually translated into transcriptional outputs thus remains unclear. Here we use a novel assay to position an enhancer at hundreds of different chromosomal sites relative to a fixed promoter and quantitatively measure promoter output.
Project description:Although the locations of promoters and enhancers have been identified in several cell types, we have yet limited information on their connectivity. We developed HiCap, which combines Hi-C with promoter sequence capture, to enable genome-wide identification of regulatory interactions with single-enhancer resolution. HiCap analyses of mouse embryonic stem cells (mESC) identified promoter-enhancer interactions predictive of gene expression change upon perturbation, opening up for genomic analyses of long-range gene regulation. HiCap was designed by combining Hi-C with with sequence capture (for all promoters) and carried out in mouse embryonic stem cells (mESC)