Facultative CTCF sites moderate mammary super-enhancer activity and regulate juxtaposed gene in non-mammary cellsopen access
- Authors
- Willi, M.; Yoo, K. H.; Reinisch, F.; Kuhns, T. M.; Lee, H. K.; Wang, C.; Hennighausen, L.
- Issue Date
- Jul-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.8
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 8
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/8260
- DOI
- 10.1038/ncomms16069
- ISSN
- 2041-1723
- Abstract
- Precise spatiotemporal gene regulation is paramount for the establishment and maintenance of cell-specific programmes. Although there is evidence that chromatin neighbourhoods, formed by the zinc-finger protein CTCF, can sequester enhancers and their target genes, there is limited in vivo evidence for CTCF demarcating super-enhancers and preventing cross talk between distinct regulatory elements. Here, we address these questions in the Wap locus with its mammary-specific super-enhancer separated by CTCF sites from widely expressed genes. Mutational analysis demonstrates that the Wap super-enhancer controls Ramp3, despite three separating CTCF sites. Their deletion in mice results in elevated expression of Ramp3 in mammary tissue through augmented promoter-enhancer interactions. Deletion of the distal CTCF-binding site results in loss of Ramp3 expression in non-mammary tissues. This suggests that CTCF sites are porous borders, allowing a super-enhancer to activate a secondary target. Likewise, CTCF sites shield a widely expressed gene from suppressive influences of a silent locus.
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