Dosage compensation in mammals: why does a gene on the inactive X yield less product than one on the active X?

An expressed gene on the inactive mammalian X chromosome yields less product than the same gene on the active X. Characteristics of the inactive X which might be responsible for this are late replication, chromatin clumping, and altered patterns of DNA methylation. If an expressed gene on the inactive X is not replicated until late in S, it will be present in two copies for a shorter fraction of the cell cycle than its early replicating homologue and therefore yield less product. Alternatively, transcription may be slowed by a microenvironment of highly condensed chromatin or by an abnormal pattern of methylation of the DNA template. Experiments are proposed by which to test these and related hypotheses.