Publication Date:
2014-07-22
Description:
Developmental enhancers initiate transcription and are fundamental to our understanding of developmental networks, evolution and disease. Despite their importance, the properties governing enhancer-promoter interactions and their dynamics during embryogenesis remain unclear. At the beta-globin locus, enhancer-promoter interactions appear dynamic and cell-type specific, whereas at the HoxD locus they are stable and ubiquitous, being present in tissues where the target genes are not expressed. The extent to which preformed enhancer-promoter conformations exist at other, more typical, loci and how transcription is eventually triggered is unclear. Here we generated a high-resolution map of enhancer three-dimensional contacts during Drosophila embryogenesis, covering two developmental stages and tissue contexts, at unprecedented resolution. Although local regulatory interactions are common, long-range interactions are highly prevalent within the compact Drosophila genome. Each enhancer contacts multiple enhancers, and promoters with similar expression, suggesting a role in their co-regulation. Notably, most interactions appear unchanged between tissue context and across development, arising before gene activation, and are frequently associated with paused RNA polymerase. Our results indicate that the general topology governing enhancer contacts is conserved from flies to humans and suggest that transcription initiates from preformed enhancer-promoter loops through release of paused polymerase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ghavi-Helm, Yad -- Klein, Felix A -- Pakozdi, Tibor -- Ciglar, Lucia -- Noordermeer, Daan -- Huber, Wolfgang -- Furlong, Eileen E M -- England -- Nature. 2014 Aug 7;512(7512):96-100. doi: 10.1038/nature13417. Epub 2014 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory, Genome Biology Unit, D-69117 Heidelberg, Germany. ; 1] European Molecular Biology Laboratory, Genome Biology Unit, D-69117 Heidelberg, Germany [2]. ; Swiss Federal Institute of Technology, School of Life Sciences, CH-1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043061" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Binding Sites
;
Chromosomes, Insect/genetics/metabolism
;
DNA-Directed RNA Polymerases/*metabolism
;
Drosophila melanogaster/embryology/*enzymology/*genetics
;
Embryonic Development/*genetics
;
Enhancer Elements, Genetic/*genetics
;
Gene Expression Regulation, Developmental/genetics
;
Genetic Loci/genetics
;
Genome, Insect/genetics
;
Humans
;
Promoter Regions, Genetic/*genetics
;
Transcription Initiation, Genetic
;
Transcriptional Activation
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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