2 - Is X-Chromosome Inactivation a Homology Effect?

Homology effect is defined as any effect on gene expression or chromosome behavior relating to the presence of homologous sequences. Using this definition, imprinted X inactivation probably does not qualify as a homology effect, since paternal silencing is strictly the result of gametic imprinting and occurs without regard to total X-chromosome number. In contrast, random X inactivation could however qualify as a homology effect for three reasons. First, X inactivation depends on the presence of more than one X homolog, or more specifically, more than one Xic sequence. Second, some form of trans-sensing must be operative at the onset of X inactivation, specifically during the process of choice, so that an XX cell does not inadvertantly designate one X as both the future active and inactive X. And finally, the fact that Xist and Tsix produce noncoding homologous RNAs conjures up an analogy to posttranscriptional gene silencing in other organisms. In this class of silencing mechanisms, the action of a transcriptionally active gene is nullified by homologous double-stranded RNA molecules produced at ectopic loci in a process referred to as “RNAi” for RNA-inhibition.