Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation

A Continuity of X-Chromosome Silence from Gamete to Zygote

“…Recent inquiries into this problem have led to some surprising and somewhat conflicting findings (Huynh and Lee 2003;Okamoto et al 2004). Here, we will focus on recent developments in the understanding of when and how dosage compensation occurs in the mammal and also highlight major differences in current thinking.…”

“…Both are controlled by a cis-acting X-inactivation center (Xic) (Brown et al 1991), a region that contains several noncoding RNA genes including Xist (Brockdorff et al 1992;Brown et al 1992) and the complementary Tsix gene (Lee et al 1999). During imprinted XCI, silencing is associated with the spread of Xist RNA along the paternal X chromosome (Mak et al 2002;Huynh and Lee 2003), while activity on the maternal X chromosome is preserved by expression of Tsix (Lee 2000;Sado et al 2001). Random XCI is also ini-tiated by Xist expression and blocked by Tsix.…”

“…In the study by our group (Huynh and Lee 2003), two techniques were used to examine the transcriptional status of the X chromosome in preimplantation embryos. To address whether nascent transcription occurs on the X P , a two-color RNA fluorescence in situ hybridization (FISH) technique was used that simultaneously detects Xist RNA and the Cot-1 RNA fraction.…”

“…First, imprinted XCI is imperfect at the chromosomal level. RT-PCR analysis of a dozen X-linked genes revealed that, while most genes examined are subject to inactivation, genes residing at either end of the X P tend to escape silencing (Huynh and Lee 2003). Of genes subject to inactivation, the degree of silencing varies depending on the location of the gene on the X P -genes residing proximal to the Xic were subject to a higher degree of silencing than genes located more distal.…”

“…Furthermore, expression is variable among blastomeres of a single embryo and among different embryos, the result of which is that X M almost never contributes 100% of transcripts for any given gene (Huynh and Lee 2003). In general, there appears to be one paternal transcript for every three to four maternal transcripts.…”