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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM076955-02
Application #
7155525
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Portnoy, Matthew
Project Start
2005-12-15
Project End
2007-12-14
Budget Start
2006-12-15
Budget End
2007-12-14
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Anguera, Montserrat C; Liu, Matthew; Avruch, Joseph et al. (2008) Characterization of two Mst1-deficient mouse models. Dev Dyn 237:3424-34
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