Coordinate control and variation in X-linked gene expression among female mice.

Abstract

In normal female mammals, one of the two X Chromosome (Chr) homologs per cell is silenced coordinately during early embryogenesis. The genes located on the inactivated X homolog are predicted to be influenced by the same underlying repression mechanism. To test the uniformity of cis-acting gene repression, 32 genetically identical F1 female mice were analyzed for differential expression of homologous alleles at three X-linked genes-Otc, Atp7a (= Mottled), and Hprt. Gene expression was assayed by the single-nucleotide primer extension (SNuPE) method, thereby allowing the three genes to be quantitated from the same RNA sample. Although variable between individual animals, the relative expression of the two alleles (allelic expression ratio) of the genes is significantly correlated within each steady-state RNA pool. When examined by animal age (3 months to 12 months), no statistically significant differences were observed in the mean or variance of allelic expression ratio. Together, the results confirm that X inactivation is coordinately controlled and is stable across the early- to mid-adult life span.