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  Topological isolation of developmental regulators in mammalian genomes

Wu, H.-J., Landshammer, A., Stamenova, E. K., Bolondi, A., Kretzmer, H., Meissner, A., et al. (2021). Topological isolation of developmental regulators in mammalian genomes. Nature Communications, 12: 4897. doi:10.1038/s41467-021-24951-7.

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Wu, Hua-Jun , Author
Landshammer, Alexandro1, Author              
Stamenova, Elena K. , Author
Bolondi, Adriano1, Author              
Kretzmer, Helene1, Author              
Meissner, Alexander1, Author              
Michor, Franziska , Author
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1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              

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 Abstract: Precise control of mammalian gene expression is facilitated through epigenetic mechanisms and nuclear organization. In particular, insulated chromosome structures are important for regulatory control, but the phenotypic consequences of their boundary disruption on developmental processes are complex and remain insufficiently understood. Here, we generated deeply sequenced Hi-C data for human pluripotent stem cells (hPSCs) that allowed us to identify CTCF loop domains that have highly conserved boundary CTCF sites and show a notable enrichment of individual developmental regulators. Importantly, perturbation of such a boundary in hPSCs interfered with proper differentiation through deregulated distal enhancer-promoter activity. Finally, we found that germline variations affecting such boundaries are subject to purifying selection and are underrepresented in the human population. Taken together, our findings highlight the importance of developmental gene isolation through chromosomal folding structures as a mechanism to ensure their proper expression.

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Language(s): eng - English
 Dates: 2021-07-122021-08-12
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: DOI: 10.1038/s41467-021-24951-7
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 Sequence Number: 4897 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723