Mammalian Development Laboratory; National Institute of Genetics
In mammals, X-chromosome inactivation (XCI) takes place in each female somatic cell and only one X chromosome remains genetically active to equalize the dosage of X-linked genes in XY male and XX female. This XCI is a multi-step process of the X-chromosome choice and counting to inactivate and the initiation and propagation of silencing, which are cis-regulated under the single chromosomal region, X-chromosome inactivation centre. In mouse, paternally derived X chromosome is preferentially chosen to inactivate in the extraembryonic tissue (imprinted XQ, while random XCI of either paternal or maternal X chromosome occurs in the embryonic tissue. To understand choice mechanism of the imprinted XCI, experimental ng/fg embryos were produced by nuclear transplantation of non-growing (ng) nucleus from oocytes before the oocyte growth stage and fully growing (fg) nucleus from oocytes after the germinal vesicle stage. In the female ng/fg embryos heterozygous for the X chromosome carrying the lacZ transgene, whose expression is linked to X-chromosome activity, lacZ expression was negative in the extra embryonic cells when 1acZ was derived from ng oocytes but not from fg oocytes. LacZ on maternal X chromosome from ng oocytes was preferentially repressed. This finding was confirmed in another experimental ng/fg embryos heterozygous for the Rb(X.9)6H translocation by the replication timing of X chromosome. Maternal X chromosome inherited from ng oocytes is rigidly chosen to replicate allocyclically in the majority of extraembryonic cells, whereas random XCI occurred in the embryonic tissues. These findings clearly indicate that X chromosome derived from ng oocytes is comparable to paternal X chromosome in an aspect of X-chromosome choosing to inactivate. It seems that X chromosome from ng oocytes is chosen to inactivate by default and X-chromosome imprint responsible for resistance to be inactivated is imposed during oocyte growth.