Dosage compensation in human pre-implantation embryos: X-chromosome inactivation or dampening?

Abstract

Recent studies support either X‐dampening or X‐inactivation as the mechanism of dosage compensation in human embryos. The data and possible underlying causes for these conflicting models are discussed here.

Figure 1. X‐chromosome dampening versus inactivation

Schematic representation of X‐chromosome dynamics in early embryonic mouse and human development. In mouse, paternal‐X (X_p) (imprinted) gets inactivated initially. Later in the epiblast progenitor cells of the late blastocyst, inactive‐X_p is reactivated. The embryo proper then undergoes random X‐inactivation. However, in humans there is no imprinted X‐inactivation. Recent studies have inferred contradictory models of X‐chromosome dynamics in human pre‐implantation embryos: X‐chromosome dampening versus inactivation. According to the dampening model, following the biallelic Xist expression initiation at the 8‐cell stage, expression of X‐linked genes is downregulated while maintaining biallelic expression until the late blastocyst stage. On the contrary, another study suggests the initiation of X‐inactivation in human pre‐implantation development as they found Xist expression was followed by a majority of X‐linked genes showing monoallelic expression.