%0 Journal Article
%T The Stability of the Induced Epigenetic Programs
%A Maria J. Barrero
%J International Journal of Genomics
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/434529
%X For many years scientists have been attracted to the possibility of changing cell identity. In the last decades seminal discoveries have shown that it is possible to reprogram somatic cells into pluripotent cells and even to transdifferentiate one cell type into another. In view of the potential applications that generating specific cell types in the laboratory can offer for cell-based therapies, the next important questions relate to the quality of the induced cell types. Importantly, epigenetic aberrations in reprogrammed cells have been correlated with defects in differentiation. Therefore, a look at the epigenome and understanding how different regulators can shape it appear fundamental to anticipate potential therapeutic pitfalls. This paper covers these epigenetic aspects in stem cells, differentiation, and reprogramming and discusses their importance for the safety of in vitro engineered cell types. 1. Introduction The genome is organized into particular chromatin structures that have specific roles both in maintaining the overall structure and in gene expression. The fundamental unit of chromatin is the nucleosome, composed of two copies each of four core histones, H2A, H2B, H3, and H4, wrapped by 146£¿bp of DNA. The recruitment of linker histone H1 and other structural proteins can lead to further condensation and the of higher-order structures, which play additional roles in the organization of chromosomes. Chromatin offers a physical barrier to the efficient recruitment and processivity of the RNA Polymerase II (Poll l) and thus impedes gene transcription [1]. The extent of chromatin condensation is subject to regulation. The N-terminal tails of histones are relatively accessible to enzymatic modifications such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation. Furthermore, the cytosine residues of DNA can be modified by methylation and hydroxymethylation. These modifications can influence the degree of condensation of chromatin per se or/and facilitate the recruitment of structural or effector proteins, such as remodeling complexes, that directly affect the condensation of chromatin. Certain areas of the genome are organized into heavily condensed chromatin structures, such as centromeric regions, and offer little room for transcriptional regulation. These areas are enriched in H3K9 methylation and marked by the presence of structural proteins such as HP1 (heterochromatin protein 1), which contribute to maintain high levels of condensation that play mainly structural roles in the organization of chromosomes.
%U http://www.hindawi.com/journals/ijg/2012/434529/