Abstract
ABSTRACTX chromosome inactivation (XCI), determined during development, remains stable after embryonic cell divisions. However, primordial germ cells (PGCs) are exceptions in that XCI is reprogrammed and inactivated X chromosomes are reactivated. Although interactions between PGCs and somatic cells are thought to be important for PGC development, little is known about them. Here, we performed imaging of X chromosome reactivation (XCR) using the ‘Momiji’ mouse system, which can monitor the X chromosome's inactive and active states using two color fluorescence reporter genes, and investigated whether interactions would affect XCR in PGCs. Based on their expression levels, we found that XCR of the Pgk1 locus began at embryonic day (E)10.5 and was almost complete by E13.5. During this period, PGCs became distributed uniformly in the genital ridge, proliferated, and formed clusters; XCR progressed accordingly. In addition, XCR of the Pgk1 locus preceded that of the Hprt locus, indicating that the timing of epigenetic memory erasure varied according to the locus of each of these X-linked genes. Our results indicate that XCR proceeds along with the proliferation of PGCs clustered within the genital ridge.This article has an associated First Person interview with the first author of the paper.
Highlights
X chromosome inactivation (XCI) is an epigenetic mechanism characteristic of Eutheria that equalizes the expression of X-linked genes between male and female mammals by inactivating one of the two X chromosomes in females
X chromosome reactivation (XCR) starts nonsynchronously and the timing varies between cells It is generally accepted that there is an interaction between the genital ridge (GR) and primordial germ cells (PGCs), so we investigated whether this would affect XCR in vivo
Based on the knowledge of PGC migration toward the GR, it seemed likely that the location and patterns of XCR among PGCs in the GR would show characteristic features depending on the timing of arrival
Summary
X chromosome inactivation (XCI) is an epigenetic mechanism characteristic of Eutheria that equalizes the expression of X-linked genes between male and female mammals by inactivating one of the two X chromosomes in females. This epigenetic silencing is established during early embryonic development and maintained stably thereafter through embryonic cell divisions. It is generally believed that XCI always occurs in differentiated cells If this mechanism fails, it leads to death during early development, so it is an important gene regulatory mechanism that requires strict control. In the mouse – the most frequently studied animal model – whether the paternally or maternally derived X chromosome is inactivated is known to change dynamically depending on developmental stages and tissues (Augui et al, 2011; Jeon et al, 2012; Kobayashi, 2017; Pasque and Plath, 2015)
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