OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publikationsserver des Helmholtz Zentrums München: X-linked deletion of <em>Crossfirre, Firre,</em> and <em>Dxz4</em> in vivo uncovers diverse phenotypes and combinatorial effects on autosomes.

PuSH - Publikationsserver des Helmholtz Zentrums München

Hasenbein, T.P.* ; Hoelzl, S.* ; Smith, Z.D.* ; Gerhardinger, C.* ; Gonner, M.O.C.* ; Aguilar-Pimentel, J.A. ; Amarie, O.V. ; Becker, L. ; Calzada-Wack, J. ; Dragano, N.R.V. ; da Silva Buttkus, P. ; Garrett, L. ; Hölter, S.M. ; Kraiger, M. ; Östereicher, M.A. ; Rathkolb, B. ; Sanz-Moreno, A. ; Spielmann, N. ; Wurst, W. ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Meissner, A.* ; Engelhardt, S.* ; Rinn, J.L.* ; Andergassen, D.*

X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes.

Nat. Commun. 15:10631 (2024)
Verlagsversion DOI PMC
Free journal
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Chromosome; Genome; Inactivation; Expression; Organization; Metabolism; Generation
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 10631 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Förderungen German Center for Diabetes Research
German Federal Ministry of Education and Research
DZHK (Junior Research Group)
BMBF
NIH
Deutsche Forschungsgemeinschaft
This work was partly supported by the Deutsche Forschungsgemeinschaft (Project-ID: 403584255-TRR 267, received by D.A. and S.E.), the NIH (P01 GM099117, received by J.L.R and A.M.), the German Federal Ministry of Education and Research (Infrafrontier gran