Histone Modifications Regulate Pluripotency in the Early Mouse Embryo
Feb 6, 2007 histones, methylation, research articles
Earlier this year, a group affiliated with Cambridge University at the Wellcome Trust/Cancer Research UK Gordon Institute reported in Nature that epigenetics, specifically methylation of certain arginine residues of histone H3, directly contribute to cell fate and success in the four-cell stage embryo in the mouse model. These findings confront the widely accepted paradigm that mammalian embryos begin development with similar, if not identical, cell types which differ only when inside and outside cells form. Furthermore, the findings solidify that epigenetic modifications influence cell direction and determination.
By investigating the belief that epigenetic mechanisms are utilized to support pluripotency, the researchers provided evidence that arginine methylation of histone H3 is at its highest in four-cell blastomeres which contribute to the inner cell mass (ICM), polar trophectoderm and fully develop when joined with chimaeras. Inversely, arginine methylation of histone H3 is lowest in cell progeny which contribute primarily to mural trophectoderm which exhibit abnormal development when joined with chimaeras. This finding indicates that maximal levels of arginine methylation of histone H3 influence blastomeres’ contribution to pluripotent cells of the inner cell mass. Furthermore, over-expression of the histone H3 arginine methyltransferase gene CARM1 in blastomeres resulted in direction of subsequent progeny cells to the ICM – solidifying the theory that “specific histone modifications are the earliest known epigenetic marker contributing to development of ICM” and precede formation of inside and outside cells.
References:
Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M. 2007. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature 445:214-218.
doi:10.1038/nature05458
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