![]() ![]() Subsequently, random XCI (rXCI see Glossary, Box 1) is initiated in cells of the embryo proper, and gives rise to individuals in whom the maternal and paternal X chromosomes are active in roughly half of the cells each ( Dupont and Gribnau, 2013).Ĭomparison of XCI timing and hallmarks between mouse and human early development. This form of X-inactivation is maintained in the extra-embryonic lineages, but reversed in the inner cell mass of early blastocysts, in which the two X chromosomes are transiently active ( Mak et al., 2004 Okamoto et al., 2004 Takagi, 2003). First, soon after fertilization and zygotic genome activation, XCI is established in an imprinted manner, with systematic inactivation of the paternal X chromosome ( Fig. 1 Mak et al., 2004 Okamoto et al., 2004). More subtle exploration revealed two waves of XCI in mouse ( Fig. 1). In the germline, however, reactivation of the X chromosome occurs concomitantly to global epigenetic reprogramming during primordial germ cell (PGC see Glossary, Box 1) specification ( Payer et al., 2011). XCI is tightly regulated, established early during embryonic development and then stably maintained for the entire in utero and adult life. Mice have long been the leading model for X-inactivation studies in placental mammals, and have thus served to elucidate the developmental regulation of this process and to identify most of the molecular mechanisms and factors involved. An lncRNA produced by the X chromosome that is retained in the nucleus and triggers XCI. Inactive X chromosome, with most genes being silenced. An originally inactive X chromosome that has been partially reactivated owing to erosion of XCI, a process that takes place spontaneously when pluripotent stem cells are grown in culture. X chromosome inactivation, the process whereby one of the two X chromosomes is transcriptionally shut down in female mammals. An lncRNA that coats active X chromosomes in early development. Chromosome domains of preferential interaction in the 3D space. Next-generation sequencing of all cellular RNAs, which can be performed on a cell population (bulk RNA-seq) or on individual cells (scRNA-seq). Random XCI results in a mosaic individual, in which the maternal X chromosome is active in roughly half of the cells and the paternal one in the other half. Refers to the equal probability of each X chromosome (maternal and paternal) to be inactivated. Precursors or primary undifferentiated stem cells that will give rise to the gametes. The property of some cells to form all somatic lineages and germ cells pluripotency exists in two states, naïve and primed, representing the distinct cellular features of the pre- and post-implantation epiblast, respectively. An RNA molecule longer than 200 nucleotides that does not encode a protein. A chromosome pair, such as the sex chromosomes X and Y, which have some homology but differ in size, shape and genetic content. Defines the morphological criteria to classify a pre-implantation embryo at different stages of its development ( Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011). It allows the embryo to take control over its development through a faithful reprogramming and restructuring of the two parental genomes before transcription occurs.ĮSHRE Istanbul consensus. A complex process occurring in the embryo after fertilization. Of note, some genes are refractory to XCI and escape this process, but the proportion of such genes varies from one species to another ( Carrel and Brown, 2017).Įmbryo genome activation (EGA). During XCI, several hundreds of physically linked loci are concomitantly and stably silenced ( Robert Finestra and Gribnau, 2017). In metatherians and eutherians, the increased dose of X-linked genes in females is compensated for by the functional exclusion of one of the two X chromosomes, a process referred to as X chromosome inactivation (XCI see Glossary, Box 1). Although this imbalance is well tolerated for the male-specific Y chromosome, probably because of its highly specialized and low gene content, this is not the case for the X chromosome, which covers ∼1.5 Mb of DNA and harbors up to a thousand genes, many of which serve fundamental cellular functions. The formation of heteromorphic (see Glossary, Box 1) sex chromosomes during the evolution of mammals has created a dosage imbalance for sex-linked genes between sexes.
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