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

Abstract

EMBO Reports (2018) e46294 Eutherian female mammals compensate the dosage of X‐linked gene expression between XY male and XX female, via transcriptional silencing of one of the two X‐chromosomes during embryonic development, a phenomenon known as X‐chromosome inactivation [1]. Studies have shown that like murine adult female somatic cells, the human counterparts also have many genes inactivated in one of the X‐chromosomes. In mouse, there are two forms of X‐inactivation: imprinted and random (Fig 1). Humans on the other hand do not undergo imprinted X‐inactivation [2]. However, X‐chromosome dynamics in human pre‐implantation embryos remains elusive, largely due to the restricted availability of human embryos and technical difficulties. Early experiments on human embryos reported conflicting results [3], [4], [5]. One study showed progressive accumulation of XIST on one of the X‐chromosomes along with the inactivation of X‐linked genes in pre‐implantation female embryos [3]. In contrast, another study reported XIST coating on both X‐chromosomes accompanied by partial exclusion of RNA‐Pol II in most early embryonic cells without the transcriptional silencing of X‐linked genes, indicating incipient X‐inactivation during pre‐implantation development. However, a minor population of cells showed monoallelic Xist expression, and the authors also reported XIST coating of the X‐chromosomes in male embryos [4]. These differences were most likely caused by differences in the sensitivity of the techniques used and/or the low numbers of X‐linked genes studied. In …