Alterations in epigenetically-regulated gene expression are critical determinants for oncogenesis, yet the molecular details involved in epigenetic programming and imprinting are not well understood. X-chromosome inactivation (XCI) is an epigenetic event where imprinting triggers transcriptional silencing of the X for equal gene dosage in female cells. The molecular details regulating XCI in the early female embryo are not well understood, and the transcriptional status of X in the preimplantation embryo has recently become a controversial topic in the field. New evidence indicates that the paternal X (XP) is transcriptionally silent in the early embryo, suggesting that the embryo may have inherited a transcriptionally silent XP with silence originating during spermatogenesis. This research proposal will determine whether a continuum of XP transcriptional silence (from spermatogenesis into the fertilized zygote) exists. The transcriptional status of X and expression levels of various X-linked genes will be determined in post-meiotic spermatids and at different developmental stages in the pre-implantation embryo. This research will provide a foundation for future investigations into epigenetically-regulated chromosomal silencing mechanisms. ? ?
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| Anguera, M C; Sun, B K; Xu, N et al. (2006) X-chromosome kiss and tell: how the Xs go their separate ways. Cold Spring Harb Symp Quant Biol 71:429-37 |
