Epigenetic reprogramming in cloned embryos
Dean W, Santos F, Stojkovic M, Zakhartchenko V, Walter J, Wolf E, Reik W
Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos.
PNAS 98: 13734-13738, 2001

In 1997, the news from Scotland made headlines throughout the world. Dr. Ian Wilmut and his colleagues reported that they succeeded to make a live cloned offspring of sheep from cultured mammary gland cells by nuclear transfer into enucleated oocyte.
This report implied that one could produce genetic copies of an individual animal. However, it was not exactly that simple. They transplanted 29 early embryos into the uterus of recipient female sheep but only one offspring was born. The fraction of embryos that completed embryonic development to term was extremely low comparing to normal development. In addition, nuclear transfer experiments on other animals such as bovine and mice also showed low success rates, with higher mortality of the offspring. These results suggested that a critical mechanism necessary to complete normal embryonic development was still missing in these nuclear transfer embryos.

The paper we are going to discuss is one of the key papers that showed critical roles of the reprogramming of genome-wide methylation in early embryos. The authors found that genome-wide reprogramming is conserved widely throughout mammalian species. Observations in normal embryos showed active demethylation of the paternal genome at the preimplantation stage, followed by de novo methylation. In contrast, demethylation and methylation profiles in cloned embryos were abnormal at the preimplantation stage, raising a possibility that altered methylation pattern in cloned embryos could be a cause of aberrant development.

Although the results presented in this paper are very important, I found many questions after reading the paper. The authors could add many additional ways to convince the readers to accept the points they claimed. In this class I would like to discuss such points with you.