| Autor: |
Tim P. Hasenbein, Sarah Hoelzl, Zachary D. Smith, Chiara Gerhardinger, Marion O. C. Gonner, Antonio Aguilar-Pimentel, Oana V. Amarie, Lore Becker, Julia Calzada-Wack, Nathalia R. V. Dragano, Patricia da Silva-Buttkus, Lillian Garrett, Sabine M. Hölter, Markus Kraiger, Manuela A. Östereicher, Birgit Rathkolb, Adrián Sanz-Moreno, Nadine Spielmann, Wolfgang Wurst, Valerie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, Alexander Meissner, Stefan Engelhardt, John L. Rinn, Daniel Andergassen |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-54673-5 |
| Popis: |
Abstract The lncRNA Crossfirre was identified as an imprinted X-linked gene, and is transcribed antisense to the trans-acting lncRNA Firre. The Firre locus forms an inactive-X-specific interaction with Dxz4, both loci providing the platform for the largest conserved chromatin structures. Here, we characterize the epigenetic profile of these loci, revealing them as the most female-specific accessible regions genome-wide. To address their in vivo role, we perform one of the largest X-linked knockout studies by deleting Crossfirre, Firre, and Dxz4 individually and in combination. Despite their distinct epigenetic features observed on the X chromosome, our allele-specific analysis uncovers these loci as dispensable for imprinted and random X chromosome inactivation. However, we provide evidence that Crossfirre affects autosomal gene regulation but only in combination with Firre. To shed light on the functional role of these sex-specific loci, we perform an extensive standardized phenotyping pipeline and uncover diverse knockout and sex-specific phenotypes. Collectively, our study provides the foundation for exploring the intricate interplay of conserved X-linked loci in vivo. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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Full text from SpringerLink