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  Defining genome architecture at base-pair resolution

Hua, P., Badat, M., Hanssen, L. L. P., Hentges, L. D., Crump, N., Downes, D. J., et al. (2021). Defining genome architecture at base-pair resolution. Nature, 595(7865), 125-129. doi:10.1038/s41586-021-03639-4.

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 Creators:
Hua, P., Author
Badat, M., Author
Hanssen, L. L. P., Author
Hentges, L. D., Author
Crump, N., Author
Downes, D. J., Author
Jeziorska, D. M., Author
Oudelaar, A. M.1, Author           
Schwessinger, R., Author
Taylor, S., Author
Milne, T. A., Author
Hughes, J. R., Author
Higgs, D. R., Author
Davies, J. O. J., Author
Affiliations:
1Lise Meitner Group Genome Organization and Regulation, MPI for Biophysical Chemistry, Max Planck Society, ou_3261271              

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Free keywords: Chromatin structure; Gene regulation
 Abstract: In higher eukaryotes, many genes are regulated by enhancers that are 104–106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7–22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.

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Language(s): eng - English
 Dates: 2021-06-092021-07-01
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41586-021-03639-4
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Title: Nature
Source Genre: Journal
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Pages: 5 Volume / Issue: 595 (7865) Sequence Number: - Start / End Page: 125 - 129 Identifier: -