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In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation

By Daniel Andergassen, Zachary D Smith, Jordan P. Lewandowski, Chiara Gerhardinger, Alexander Meissner, John L. Rinn

Posted 18 Apr 2019
bioRxiv DOI: 10.1101/612440 (published DOI: 10.7554/eLife.47214)

Recent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 alleles are not required for X chromosome inactivation (XCI) in cell lines. Here we determined the in vivo contribution of these alleles by generating mice carrying a single or double deletion of Firre and Dxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, and Firre locus dependent gene sets. The largest transcriptional effect was observed in all strains lacking the Firre locus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology.

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