Abstract
The regulation of the genome relies on the overlying epigenome to instruct, define, and restrict the activities of cellular differentiation and growth integral to embryonic development, as well as defining the key activities of terminally differentiated cell types. These instructions are positioned as readers, writers, and erasers in their functional roles. Among the sizeable repertoire of epigenetic instructions, DNA methylation is perhaps the best understood process. In mammals, multiple cycles of reprogramming, the addition and removal of DNA methylation coupled with modulation of chromatin post-translational modifications (PMTs), constitute critical phases when the developing embryo must negotiate lineage specification and commitment events which serve to canalise development. During these reprogramming events the DNA methylation instruction is often removed, thereby allowing a change in developmental restriction, resulting in a return to a more plastic and pluripotent state. Thus, in germline reprogramming, DNA demethylation is essential in order to give rise to fully functional gametes which are inherited across generations and poised to restore totipotency. A similar return to a less differentiated state can also be achieved experimentally. DNA methylation constitutes one of the significant barriers to erroneous induced pluripotency, and loss of DNA methylation is a prerequisite for the generation of induced pluripotent stem cells (iPSCs). Taking fully differentiated cells, such as skin fibroblast cells or peripheral blood cells, and turning back the developmental clock by generating iPSCs constituted a technological breakthrough in 2006, offering unprecedented promise in precision regenerative medicine. In this chapter, I will explore mechanistic possibilities for DNA demethylation in the context of natural and experimentally induced epigenetic reprogramming. The balance of the maintenance of DNA methylation as a heritable mark together with its potential for timely removal is essential for lifelong health and may be key in our understanding of aging and the potential to limit or reverse that process.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.