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  Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Aljahani, A., Hua, P., Karpinska, M. A., Quililan, K., Davies, J. O. J., & Oudelaar, A. M. (2022). Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF. Nature Communications, 13: 2139. doi:10.1038/s41467-022-29696-5.

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 Creators:
Aljahani, A.1, Author              
Hua, P., Author
Karpinska, M. A.1, Author              
Quililan, K.1, Author              
Davies, J. O. J., Author
Oudelaar, A. M.1, Author              
Affiliations:
1Lise Meitner Group Genome Organization and Regulation, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, ou_3350292              

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Free keywords: Chromatin structure; Gene regulation
 Abstract: Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.

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Language(s): eng - English
 Dates: 2022-04-19
 Publication Status: Published online
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-022-29696-5
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Title: Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 13 Sequence Number: 2139 Start / End Page: - Identifier: -