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@ARTICLE{Hasenbein:273928,
author = {Hasenbein, Tim P and Hoelzl, Sarah and Smith, Zachary D and
Gerhardinger, Chiara and Gonner, Marion O C and
Aguilar-Pimentel, Antonio and Amarie, Oana V and Becker,
Lore and Calzada-Wack, Julia and Dragano, Nathalia R V and
da Silva-Buttkus, Patricia and Garrett, Lillian and Hölter,
Sabine M and Kraiger, Markus and Östereicher, Manuela A and
Rathkolb, Birgit and Sanz-Moreno, Adrián and Spielmann,
Nadine and Wurst, Wolfgang and Gailus-Durner, Valerie and
Fuchs, Helmut and Hrabě de Angelis, Martin and Meissner,
Alexander and Engelhardt, Stefan and Rinn, John L and
Andergassen, Daniel},
title = {{X}-linked deletion of {C}rossfirre, {F}irre, and {D}xz4 in
vivo uncovers diverse phenotypes and combinatorial effects
on autosomes.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-01402},
pages = {10631},
year = {2024},
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.},
keywords = {Animals / RNA, Long Noncoding: genetics / RNA, Long
Noncoding: metabolism / Female / Male / Phenotype / X
Chromosome Inactivation: genetics / Genes, X-Linked / X
Chromosome: genetics / Genomic Imprinting / Mice / Mice,
Knockout / Epigenesis, Genetic / Alleles / Mice, Inbred
C57BL / RNA, Long Noncoding (NLM Chemicals)},
cin = {AG Wurst},
ddc = {500},
cid = {I:(DE-2719)1140001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39638999},
pmc = {pmc:PMC11621363},
doi = {10.1038/s41467-024-54673-5},
url = {https://pub.dzne.de/record/273928},
}