Nuclear Cloning and Epigenetic Reprogramming of the Genome
William M. Rideout III,1
Kevin Eggan,12
Rudolf Jaenisch12*
Cloning of mammals by nuclear transfer (NT)
results in gestational or neonatal failure with at most a few percent
of manipulated embryos resulting in live births. Many of those that
survive to term succumb to a variety of abnormalities that are likely
due to inappropriate epigenetic reprogramming. Cloned embryos derived from donors, such as embryonic stem cells, that may require little or
no reprogramming of early developmental genes develop substantially better beyond implantation than NT clones derived from somatic cells.
Although recent experiments have demonstrated normal reprogramming of
telomere length and X chromosome inactivation, epigenetic information established during gametogenesis, such as gametic imprints, cannot be
restored after nuclear transfer. Survival of cloned animals to birth
and beyond, despite substantial transcriptional dysregulation, is
consistent with mammalian development being rather tolerant to
epigenetic abnormalities, with lethality resulting only beyond a
threshold of faulty gene reprogramming encompassing multiple loci.
1 Whitehead Institute for Biomedical Research
and
2 Department of Biology, Massachusetts Institute
of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
*
To whom correspondence should be addressed. E-mail:
jaenisch{at}wi.mit.edu
