Diploid analyzes DNA methylation (mDNA). Although it consists of a single carbon atom and a few hydrogens, the elusive methyl tag is an essential and fundamental part of DNA.
Genetics alone is weird if we think about it carefully. Our bodies and our health are constantly changing and DNAm is the central switch for our cells. MDNA can turn genes on or off, and that is why one genome can become hundreds of cell types. It also responds to changes in internal health as we age and external factors in our lifestyles.
The last biomarker. Unlike other epigenetic mechanisms, mDNA is highly stable and can be deciphered using next-generation sequencing. This means that we can get high-quality, high-performance data. In conclusion, we analyze a simple, broad, easy to read, and highly sensitive biomarker that is uniquely positioned at the intersection of the environment (exposome) and genetics.
The Impact of Epigenetics
In eukaryotes, gene expression is regulated at the chromatin level by epigenetics, defined as inheritable changes in gene expression without alteration of the underlying DNA nucleotide sequence (Jaenisch & Bird, 2003; Im & Shin, 2015). These changes remain when cells divide mitotically and meiotically and often last for several generations. Major epigenetic marks result in DNA methylation, histone modifications, and chromatin remodeling which, in turn, modify the accessibility of genes to transcription factors and other modulators (Qiu, 2006; Eslaminejad et al ., 2013). These modifications regulate gene expression, as well as another genomic function, by changing the local configuration of chromatin or nuclear architecture (Huang et al., 2015).
Epigenetics and Stem Cells
Analysis of the behavior of stem cells has suggested that, in addition to transcriptional regulation, genomes have a greater epigenetic alteration during embryonic development and maintenance of adult tissue (Reik, 2007). The study of epigenetic mechanisms that regulate stem cell biology had provided important insights into the unique properties of embryonic and adult stem cells (Lunyak and Rosenfeld, 2008). An intriguing study reported that both Dnmt1 and Dnmt3a; Dnmt3b ESC murine double mutants showed normal biological characteristics when cultured under undifferentiated conditions. In contrast, these cells are unable to activate the differentiation program, after an appropriate in vitro condition, as a result of Dnmt's inability to suppress pluripotent geness such as OCT4 and NANOG (Wu and Sun, 2006). These findings suggest that the alteration of chromatin structure, induced by DNA methylation, plays a key role in controlling the pattern of gene expression (Lunyak and Rosenfeld, 2008). stem cell multipotency is reduced. Genes active in the foregoing parents are progressively silenced in later developmental stages, while subsets of cell-type-specific genes are turned on. Consequently, during cell differentiation, chromatin restructuring was observed, as evidenced by the change in the location of heterochromatic markers (eg, HP1 proteins; Meshorer and Misteli, 2006; Lunyak and Rosenfeld, 2008).
Epigenetic Regulation of Genes
Epigenetic regulation of the gene commonly refers to an inheritable and long-lasting process by which gene expression is managed at the chromatin level without alterations in the DNA sequence. Epigenetics is considered a bridge between genotype and phenotype and provides a framework to regulate key biological characteristics such as cell differentiation, development, and tissue regeneration (Reik, 2007; Im and Shin, 2015). The epigenetic landscape reflects the dynamic structure of chromatin that restricts and allows access by the transcriptional apparatus to genes. Echromatin is the least condensed and most accessible form of chromatin associated with gene transcription; On the other hand, heterochromatin is the very compact chromatin that physically restricts access to transcription factors. The dynamic balance between echromatin and heterochromatin is subject to various forms of epigenetic regulation, such as DNA methylation, histone modifications, chromatin remodeling, and microRNA (miRNA; Fig. 1; Han and Yoon, 2012). . These mechanisms are considered epigenetic marks that allow to coordinate transcription programs.
Epigenetics and MSCs
The great promise of MSCs for clinical treatments of many human diseases, such as bone defects, cartilage deterioration, cardiovascular and metabolic diseases, and cerebral ischemia, has focused the attention of doctors and researchers (Tevenet al., 2011). The high number of MSCs required for therapeutic application led to an in-depth analysis of in vitro expansion procedures, as it has been widely documented that long-term culture can cause morphological and functional changes that affect the cell biology known as " replicative senescence "(Wagner, 2012; Galderisi and Giordano, 2014). Interestingly, the replicative senescence of the MSCs shows a reduced potential for differentiation and a progressive loss of proliferation capacity, although their karyotype and genomic stability are maintained. These issues fuel the debate due to the high demands for standardization and safety in regenerative medicine. Thus, the analysis of possible alterations of the epigenetic regulatory pattern of MSC during extended in vitro culture represents a burning issue that must be addressed. Histonic modifications and chromatin remodeling appear to be involved in variable cell behavior after extended culture. We demonstrate that the SWI / SNF chromatin remodeling complex plays a key role in the biology of MSC. The altered expression (up or down regulation) of BRG1, which is the ATPase subunit of the complex, promoted the senescence of MSCs with the suppression of NANOG transcription, a component of the transcriptional circuit that governs the functions of stem cells ( Squillaro et al., 2015b).