Latham K E, Patel B, Bautista F D, Hawes S M
The Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Biol Reprod. 2000 Jul;63(1):64-73. doi: 10.1095/biolreprod63.1.64.
Diploid androgenetic mouse embryos, possessing two sets of paternally inherited chromosomes, and control fertilized embryos were used to examine the relative effects of X chromosome number and parental chromosome origin on androgenone viability and X-linked gene expression. A significant difference in efficiency of blastocyst formation was observed between XX and XY androgenones in some experiments, but this difference was not uniformly observed. Significant effects of both X chromosome number and parental origin on X-linked gene expression were observed. Male and female control embryos expressed the XIST: RNA initially. This expression was followed by a preferential reduction in XIST: RNA abundance in male embryos, indicating that dosage compensation for the X chromosome may normally require the downregulation of XIST: RNA expression in male embryos, in conjunction with the production of stable XIST: transcripts in female embryos. By the late blastocyst stage, XX control embryos expressed significantly more XIST: RNA than did XY embryos. Unlike their normal counterparts, XX androgenones did not express significantly more XIST: RNA than did XY androgenones at the late blastocyst stage. Androgenones exhibited severe repression of the Pgk1 gene, but during development to the late blastocyst stage Pgk1 mRNA expression increased in XX androgenones and decreased in XY androgenones. Thus, the initial repression of the Pgk1 gene in XX androgenones was lost as the XIST: RNA declined in abundance, and this loss was correlated with a failure of XX androgenones to express significantly more XIST: RNA than did XY androgenones. These results indicate that androgenones may lack a factor that is expressed from the maternal genome and required for dosage compensation in preimplantation embryos. The results also indicate that early dosage compensation in preimplantation embryos may normally be reversible, thus providing flexibility to meet different developmental requirements of the embryonic and extraembryonic lineages.
具有两套父系遗传染色体的二倍体孤雄小鼠胚胎和对照受精胚胎被用于研究X染色体数目和亲本染色体来源对孤雄胚生存能力及X连锁基因表达的相对影响。在一些实验中，观察到XX和XY孤雄胚在囊胚形成效率上存在显著差异，但这种差异并非始终存在。观察到X染色体数目和亲本来源对X连锁基因表达均有显著影响。雄性和雌性对照胚胎最初表达XIST RNA。随后，雄性胚胎中XIST RNA丰度出现优先降低，这表明X染色体的剂量补偿通常可能需要雄性胚胎中XIST RNA表达下调，同时雌性胚胎中产生稳定的XIST转录本。到囊胚晚期，XX对照胚胎表达的XIST RNA明显多于XY胚胎。与正常对应胚胎不同，XX孤雄胚在囊胚晚期表达的XIST RNA并不比XY孤雄胚显著更多。孤雄胚表现出对Pgk1基因的严重抑制，但在发育至囊胚晚期的过程中，XX孤雄胚中Pgk1 mRNA表达增加，而XY孤雄胚中则减少。因此，随着XIST RNA丰度下降，XX孤雄胚中Pgk1基因的初始抑制作用消失，这种消失与XX孤雄胚表达的XIST RNA不比XY孤雄胚显著更多相关。这些结果表明，孤雄胚可能缺乏一种由母本基因组表达且在植入前胚胎剂量补偿中必需的因子。结果还表明，植入前胚胎的早期剂量补偿通常可能是可逆的，从而为满足胚胎和胚外谱系不同的发育需求提供灵活性。
