%0 Journal Article
%A Hasenbein, Tim P
%A Hoelzl, Sarah
%A Smith, Zachary D
%A Gerhardinger, Chiara
%A Gonner, Marion O C
%A Aguilar-Pimentel, Antonio
%A Amarie, Oana V
%A Becker, Lore
%A Calzada-Wack, Julia
%A Dragano, Nathalia R V
%A da Silva-Buttkus, Patricia
%A Garrett, Lillian
%A Hölter, Sabine M
%A Kraiger, Markus
%A Östereicher, Manuela A
%A Rathkolb, Birgit
%A Sanz-Moreno, Adrián
%A Spielmann, Nadine
%A Wurst, Wolfgang
%A Gailus-Durner, Valerie
%A Fuchs, Helmut
%A Hrabě de Angelis, Martin
%A Meissner, Alexander
%A Engelhardt, Stefan
%A Rinn, John L
%A Andergassen, Daniel
%T X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes.
%J Nature Communications
%V 15
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DZNE-2024-01402
%P 10631
%D 2024
%X 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.
%K Animals
%K RNA, Long Noncoding: genetics
%K RNA, Long Noncoding: metabolism
%K Female
%K Male
%K Phenotype
%K X Chromosome Inactivation: genetics
%K Genes, X-Linked
%K X Chromosome: genetics
%K Genomic Imprinting
%K Mice
%K Mice, Knockout
%K Epigenesis, Genetic
%K Alleles
%K Mice, Inbred C57BL
%K RNA, Long Noncoding (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39638999
%2 pmc:PMC11621363
%R 10.1038/s41467-024-54673-5
%U https://pub.dzne.de/record/273928