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000273928 041__ $$aEnglish
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000273928 1001_ $$00000-0001-7028-6559$$aHasenbein, Tim P$$b0
000273928 245__ $$aX-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes.
000273928 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000273928 520__ $$aThe lncRNA Crossfirre was identified as an imprinted X-linked gene, and is transcribed antisense to the trans-acting lncRNA Firre. The Firre locus forms an inactive-X-specific interaction with Dxz4, both loci providing the platform for the largest conserved chromatin structures. Here, we characterize the epigenetic profile of these loci, revealing them as the most female-specific accessible regions genome-wide. To address their in vivo role, we perform one of the largest X-linked knockout studies by deleting Crossfirre, Firre, and Dxz4 individually and in combination. Despite their distinct epigenetic features observed on the X chromosome, our allele-specific analysis uncovers these loci as dispensable for imprinted and random X chromosome inactivation. However, we provide evidence that Crossfirre affects autosomal gene regulation but only in combination with Firre. To shed light on the functional role of these sex-specific loci, we perform an extensive standardized phenotyping pipeline and uncover diverse knockout and sex-specific phenotypes. Collectively, our study provides the foundation for exploring the intricate interplay of conserved X-linked loci in vivo.
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000273928 650_7 $$2NLM Chemicals$$aRNA, Long Noncoding
000273928 650_2 $$2MeSH$$aAnimals
000273928 650_2 $$2MeSH$$aRNA, Long Noncoding: genetics
000273928 650_2 $$2MeSH$$aRNA, Long Noncoding: metabolism
000273928 650_2 $$2MeSH$$aFemale
000273928 650_2 $$2MeSH$$aMale
000273928 650_2 $$2MeSH$$aPhenotype
000273928 650_2 $$2MeSH$$aX Chromosome Inactivation: genetics
000273928 650_2 $$2MeSH$$aGenes, X-Linked
000273928 650_2 $$2MeSH$$aX Chromosome: genetics
000273928 650_2 $$2MeSH$$aGenomic Imprinting
000273928 650_2 $$2MeSH$$aMice
000273928 650_2 $$2MeSH$$aMice, Knockout
000273928 650_2 $$2MeSH$$aEpigenesis, Genetic
000273928 650_2 $$2MeSH$$aAlleles
000273928 650_2 $$2MeSH$$aMice, Inbred C57BL
000273928 7001_ $$00000-0003-0308-8522$$aHoelzl, Sarah$$b1
000273928 7001_ $$00000-0002-9283-1957$$aSmith, Zachary D$$b2
000273928 7001_ $$00000-0002-6113-0381$$aGerhardinger, Chiara$$b3
000273928 7001_ $$aGonner, Marion O C$$b4
000273928 7001_ $$aAguilar-Pimentel, Antonio$$b5
000273928 7001_ $$00000-0003-1705-6812$$aAmarie, Oana V$$b6
000273928 7001_ $$00000-0002-6890-4984$$aBecker, Lore$$b7
000273928 7001_ $$aCalzada-Wack, Julia$$b8
000273928 7001_ $$aDragano, Nathalia R V$$b9
000273928 7001_ $$ada Silva-Buttkus, Patricia$$b10
000273928 7001_ $$aGarrett, Lillian$$b11
000273928 7001_ $$00000-0003-4878-5241$$aHölter, Sabine M$$b12
000273928 7001_ $$00000-0002-0839-2761$$aKraiger, Markus$$b13
000273928 7001_ $$aÖstereicher, Manuela A$$b14
000273928 7001_ $$00000-0003-1239-0547$$aRathkolb, Birgit$$b15
000273928 7001_ $$00000-0001-9478-5432$$aSanz-Moreno, Adrián$$b16
000273928 7001_ $$aSpielmann, Nadine$$b17
000273928 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b18
000273928 7001_ $$00000-0002-6076-0111$$aGailus-Durner, Valerie$$b19
000273928 7001_ $$aFuchs, Helmut$$b20
000273928 7001_ $$aHrabě de Angelis, Martin$$b21
000273928 7001_ $$00000-0001-8646-7469$$aMeissner, Alexander$$b22
000273928 7001_ $$00000-0001-5378-8661$$aEngelhardt, Stefan$$b23
000273928 7001_ $$00000-0002-7231-7539$$aRinn, John L$$b24
000273928 7001_ $$00000-0003-1196-4289$$aAndergassen, Daniel$$b25
000273928 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-54673-5$$gVol. 15, no. 1, p. 10631$$n1$$p10631$$tNature Communications$$v15$$x2041-1723$$y2024
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