Abstract
The nucleus of a differentiated cell can be reprogrammed to a totipotent state by exposure to the cytoplasm of an enucleated oocyte, and the reconstructed nuclear transfer embryo can give rise to an entire organism. Somatic cell nuclear transfer (SCNT) has important implications in animal biotechnology and provides a unique model for studying epigenetic barriers to successful nuclear reprogramming and for testing novel concepts to overcome them. While initial strategies aimed at modulating the global DNA methylation level and states of various histone protein modifications, recent studies use evidence-based approaches to influence specific epigenetic mechanisms in a targeted manner. In this review, we describe—based on the growing number of reports published during recent decades—in detail where, when, and how manipulations of the epigenome of donor cells and reconstructed SCNT embryos can be performed to optimize the process of molecular reprogramming and the outcome of nuclear transfer cloning.
Highlights
The genome sequence includes the principal instructions to build, develop, and maintain an organism, but epigenetic mechanisms determine how this information is used in specific cell types during development and differentiation as well as in physiological and pathological processes
Nuclear transfer (NT) experiments were originally designed to answer one of the most intriguing questions of developmental biology: is embryonic development and differentiation and subsequent fetal growth associated with irreversible modifications in the resulting somatic cells? NT experiments were first performed in amphibians, where transfer of a differentiated cell into an enucleated oocyte resulted in the development of an adult animal, demonstrating that totipotency of somatic cells can be restored [2]
We describe and discuss in detail where, when and how these manipulations may occur and show examples of global and specific manipulations of the epigenome of nuclear donor cells or somatic cell nuclear transfer (SCNT) embryos from the growing number of reports published during the last decades
Summary
The genome sequence includes the principal instructions to build, develop, and maintain an organism, but epigenetic mechanisms determine how this information is used in specific cell types during development and differentiation as well as in physiological and pathological processes. Surviving animals often exhibit various abnormalities, such as large offspring syndrome (LOS), enlarged placentas and organ defects (observed in cattle, sheep and mice), or obesity in mouse and abnormal teat numbers and cleft lips in pigs [4,20,21,22,23]. The causes of these abnormalities can be divided into four main categories: trauma during micromanipulation, insufficient reprogramming competence of the used oocytes, resistance to reprogramming of the used donor nuclei, and anomalies induced by in vitro culture of the reconstructed. We discuss the future perspectives of manipulating the epigenome for improving cloning efficiency
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