Cohesin is required for long-range enhancer action at the Shh locus
| Autor: | Lauren Kane, Iain Williamson, Ilya M. Flyamer, Yatendra Kumar, Robert E. Hill, Laura A. Lettice, Wendy A. Bickmore |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Mammals
Cell Cycle Proteins/genetics CCCTC-Binding Factor Chromosomal Proteins Non-Histone Chromatin/genetics Enhancer Elements Genetic/genetics Cell Cycle Proteins Hedgehog Proteins/genetics Mammals/genetics CCCTC-Binding Factor/genetics Chromatin Article Chromosomal Proteins Non-Histone/genetics Mice Enhancer Elements Genetic Structural Biology Animals Hedgehog Proteins Transcription Factors/metabolism Molecular Biology Transcription Factors |
| Zdroj: | Kane, L, Williamson, I, Flyamer, I, Kumar, Y, Hill, R E, Lettice, L A & Bickmore, W A 2022, ' Cohesin is required for long-range enhancer action at the Shh locus ', Nature Structural & Molecular Biology, vol. 29, no. 9, pp. 891-897 . https://doi.org/10.1038/s41594-022-00821-8 Nat Struct Mol Biol |
| Popis: | The regulatory landscapes of developmental genes in mammals can be complex, with enhancers spread over many hundreds of kilobases. It has been suggested that three-dimensional genome organisation, particularly topologically associating domains formed by cohesin-mediated loop extrusion, are important for enhancers to act over such large genomic distances. By coupling acute protein degradation with synthetic activation by targeted transcription factor recruitment, here we show that cohesin, but not CTCF, is required for activation of a target gene – Shh - by distant enhancers in mouse embryonic stem cells. Cohesin is not required for activation directly at the promoter or from an enhancer located closer to the Shh gene. Our findings support the hypothesis that chromatin compaction mediated by cohesin-mediated loop extrusion allows for genes to be activated by enhancers that are located many hundreds of kilobases away in the linear genome but suggests that cohesin is dispensable for more genomically close enhancers. |
| Databáze: | OpenAIRE |
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