In vivo FirreandDxz4deletion elucidates roles for autosomal gene regulation

Abstract

AbstractRecent evidence has determined that the conserved X chromosome “mega-structures” controlled by theFirreandDxz4alleles are not required for X chromosome inactivation (XCI) in cell lines. Here we determined thein vivocontribution of these alleles by generating mice carrying a single or double deletion ofFirreandDxz4. 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, andFirrelocus dependent gene sets. The largest transcriptional effect was observed in all strains lacking theFirrelocus, 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.