- Somatic cell nuclear transfer experiments have also unambiguously demonstrated that reprogramming to a pluripotent state requires large-scale epigenetic changes within the cell.
On a larger scale, epigenetic analyses of normal and tumor cells have recently revealed a wide array of changes in genetic activity in cells that have undergone cancerous transformation [ 48].
High-throughput screenings identified hundreds of somatic mutations (e.g., [ 1, 2]), thousands of gene and microRNA expression changes (e.g., [ 3, 4]) and copy number variations (e.g., [ 5]), large-scale epigenetic variations (e.g., [ 6]) in a typical cancer cell.
Zouridis, H. et al. Methylation subtypes and large-scale epigenetic alterations in gastric cancer.
Although studies in this area remain at their infancy, it becomes clear that large-scale epigenetic reprograming, involving RNA-directed DNA methylation, chromatin modifications, and nucleosome remodeling, contributes to the establishment of transcriptionally repressive or permissive epigenetic landscapes.
We describe how large-scale epigenetic studies of twins can improve our understanding of how genetic, environmental and stochastic factors impact upon epigenetics, and how such studies can provide a comprehensive understanding of how epigenetic variation affects complex traits.
Second, utilizing easily accessible leukocyte DNAs, rather than pancreatic tissue- or juice-based substrate, is amenable to large-scale epigenetic epidemiology applications such as epigenome-wide association study.
Furthermore, several large-scale epigenetic studies in existing twin cohorts are already under way.
Thus, following the process of SSCs dedifferentiation back to gonocytes/PGCs and transdifferentiation into oocytes, the X chromosome might be subjected to large scale changes in gene expression and epigenetic modifications.
These large scale morphological changes are accompanied by mineralogical and crystallographic changes (Fig. 1I L ).
At such a large scale even small changes matter.
