Genetic and parent-of-origin influences on X chromosome choice in Xce heterozygous mice.
X chromosome inactivation is unique among dosage compensation mechanisms in that the two X chromosomes in females are treated differently within the same cell; one X chromosome is stably silenced while the other remains active. It is widely believed that, when X inactivation is initiated, each cell makes a random choice of which X chromosome will be silenced. In mice, only one genetic locus, the X-linked X controlling element (X ce), is known to influence this choice, because animals that are heterozygous at X ce have X-inactivation patterns that differ markedly from a mean of 0.50. To document other genetic and epigenetic influences on choice, we have performed a population-based study of the effect of X ce genotype on X-inactivation patterns. In B 6 CAST F(1) females (X ce(b)/X ce(c)), the X-inactivation pattern followed a symmetric distribution with a mean of 0.29 (SD=0.08). Surprisingly, however, in a population of X ce(b)/X ce(c) heterozygous B 6 CAST F(2) females, we observed significant differences in both the mean (p=0.004) and variance (p=0.004) of the X-inactivation patterns. This finding is incompatible with a single-locus model and suggests that additional genetic factors also influence X chromosome choice. We show that both parent-of-origin and naturally occurring genetic variation at autosomal loci contribute to these differences. Taken together, these data reveal further genetic complexity in this epigenetic control pathway.
Chadwick
Lisa Helbling
LH
Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina 27708, USA.
Willard
Huntington F
HF
D000818:Animals; D003433:Crosses, Genetic; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D017931:DNA Primers; D050172:Genes, X-Linked / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D040582:Inheritance Patterns / Q000235:genetics*; D051379:Mice; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
D017931:DNA Primers; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase