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  Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes

Ringel, A., Szabo, Q., Chiariello, A. M., Chudzik, K., Schöpflin, R., Rothe, P., et al. (2022). Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes. Cell, 185(20), 3689-3704. doi:10.1016/j.cell.2022.09.006.

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 Creators:
Ringel, Alessa1, Author           
Szabo, Quentin , Author
Chiariello, Andrea M. , Author
Chudzik, Konrad1, Author           
Schöpflin, Robert1, Author           
Rothe, Patricia1, Author
Mattei, Alexandra L.2, Author           
Zehnder, Tobias3, Author           
Harnett, Dermot , Author
Laupert, Verena3, Author           
Bianco, Simona, Author
Hetzel, Sara2, Author           
Glaser, Juliane1, Author           
Phan, Mai H. Q.1, Author           
Schindler, Magdalena1, Author           
Ibrahim, Daniel M.1, Author           
Paliou, Christina, Author
Esposito, Andrea , Author
Prada-Medina, César A.4, Author           
Haas, Stefan A.5, Author           
Giere, Peter , AuthorVingron, Martin3, Author           Wittler, Lars6, Author           Meissner, Alexander2, Author           Nicodemi, Mario , AuthorCavalli, Giacomo , AuthorBantignies, Frédéric , AuthorMundlos, Stefan1, Author           Robson, Michael I.1, Author            more..
Affiliations:
1Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433557              
2Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
3Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              
4Human Molecular Genomics (Malte Spielmann), Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_3014183              
5Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
6Dept. of Developmental Genetics (Head: Bernhard G. Herrmann), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433548              

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Free keywords: topologically associating domains lamina-associated domain enhancer-promoter specificity DNA methylation developmental gene regulation evolution loop extrusion cohesin CTCF 3D genome organization
 Abstract: Regulatory landscapes drive complex developmental gene expression, but it remains unclear how their integrity is maintained when incorporating novel genes and functions during evolution. Here, we investigated how a placental mammal-specific gene, Zfp42, emerged in an ancient vertebrate topologically associated domain (TAD) without adopting or disrupting the conserved expression of its gene, Fat1. In ESCs, physical TAD partitioning separates Zfp42 and Fat1 with distinct local enhancers that drive their independent expression. This separation is driven by chromatin activity and not CTCF/cohesin. In contrast, in embryonic limbs, inactive Zfp42 shares Fat1’s intact TAD without responding to active Fat1 enhancers. However, neither Fat1 enhancer-incompatibility nor nuclear envelope-attachment account for Zfp42’s unresponsiveness. Rather, Zfp42’s promoter is rendered inert to enhancers by context-dependent DNA methylation. Thus, diverse mechanisms enabled the integration of independent Zfp42 regulation in the Fat1 locus. Critically, such regulatory complexity appears common in evolution as, genome wide, most TADs contain multiple independently expressed genes.

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Language(s): eng - English
 Dates: 2022-09-29
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.cell.2022.09.006
 Degree: -

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 185 (20) Sequence Number: - Start / End Page: 3689 - 3704 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183