Epigenetic Modification is Central to Genome Reprogramming in Somatic Cell Nuclear Transfer

¹ Centre for Stem Cell Biology and Developmental Genetics and Institute of Human Genetics, University of Newcastle, Central Parkway, Newcastle upon Tyne, NE1 3BZ, United Kingdom
² Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, United Kingdom

^* To whom correspondence should be addressed. E-mail: Lyle.Armstrong{at}ncl.ac.uk.

	Abstract

The recent high profile reports of the derivation of human embryonic stem cells from human blastocysts produced by somatic cell nuclear transfer have highlighted the possibility of making autologous cell lines specific to individual patients. Cell replacement therapies have much potential for the treatment of diverse conditions and differentiation of embryonic stem cells is highly desirable as a means of producing the ranges of cell types required. However, given the range of immunophenotypes of embryonic stem cell lines currently available, rejection of the differentiated cells by the host is a potentially serious problem. Somatic cell nuclear transfer offers a means of circumventing this by producing embryonic stem cells of the same genotype as the donor. However, this technique is not without problems since it requires resetting of the gene expression program of a somatic cell to a state consistent with embryonic development. Some remodelling of parental DNA does occur within the fertilised oocyte but the somatic genome presented in a radically different format to those of the gametes. Hence it is perhaps unsurprising that many genes are expressed aberrantly within ‘cloned’ embryos and the ES cells derived from them. Epigenetic modification of the genome through DNA methylation and covalent modification of the histones which form the nucleosome is the key to the maintenance of the differentiated state of the cell, and it is this which must be reset during somatic cell nuclear transfer. This review focuses on the mechanisms by which this is achieved and how this may account for its partial failure in the ‘cloning’ process. We also highlight the potential dangers this may introduce into ES cells produced by this technology.