br Conclusion In conclusion DNA
Conclusion In conclusion, DNA methylation is a major epigenetic mark, which regulates temporal and spatial expression of the testicular genes required for normal spermatogenesis process. There are two types of methylation, maintenance and de novo methylation, which are catalysed by DNMT1, DNMT3A and DNMT3B enzymes, respectively. The lack of DNMTs leads to embryonic lethality, abnormal imprinting genes expression, loss of global DNA methylation levels and syndromes such as immunodeficiency, centromere instability and facial anomalies based on the lost DNMT type. The expression patterns of the DNMTs at mRNA and protein levels have been generally characterized in the spermatogenetic cell types in mice and humans. However, the molecular mechanisms regulating the DNMTs in the male germ cells are not fully understood. Also, there are a limited number of studies aimed to determine the relationship between DNMTs and male infertility development. New technologies such as genome-wide analysis enable us to assess many imprinted genes, other genes and repetitive regions, in which possible alterations may lead to male infertility development. Therefore, we think that new studies are necessary related to characterizing the potential effects of the abnormal expression of the DNMTs and subsequently appearing aberrant DNA methylation on regulating the testicular genes.
Introduction As an epigenetic modification in genomes, DNA methylation is a process in which a methyl group can be transferred from S-adenosylmethionine (SAM) to topoisomerase inhibitor or cytosine bases in the specific DNA nucleotides and plays a critical role in gene regulation (Noyer et al., 1993; Okano et al., 1999; Palmer and Marinus, 1994). Recent research also demonstrates that DNA methylation is concerned with pathogenesis of various human diseases (Laird, 2003; Lyko et al., 2005). Since DNA methylation is catalyzed by DNA methyltransferase (MTase) and abnormalities in DNA MTase activity usually occur before other signs of malignancy, DNA MTase has been regarded as a predictive biomarker and therapeutic target in the diagnosis and treatment of various diseases (Robertson, 2005; Mutze et al., 2011). Therefore, sensitive and accurate method for the DNA MTase assay is highly desirable, which may provide an applicable approach for early diagnosis and drug discovery. Conventional methods for the DNA MTase assay include high-performance liquid chromatography (HPLC), gel electrophoresis, and radioactive labeling strategy, which usually suffer from the disadvantages of laborious operation, radioactive hazard and expensive equipment (Zeng et al., 2013). Such limitations have promoted the development of new methods for determination of DNA MTase activity, such as fluorescent (Ouyang et al., 2012), colorimetric ( Y. X. Zhao et al., 2014; Wu et al., 2013), electrochemical (EC) (Su et al., 2012; Zhang et al., 2015), and electrochemiluminescent (Li et al., 2012) methods. Among these methods, EC DNA MTase assay has attracted increasing attention by virtue of its low cost, high sensitivity, fast, and relatively portable devices. The assay is mainly based on a well-designed system, in which DNA MTase can specifically act on the corresponding DNA recognition sites for DNA methylation and followed with the methylation-sensitive restriction enzyme cleavage. To improve the sensitivity, various nanomaterials have been adopted in DNA MTase activity assay. Metal-organic frameworks (MOFs) are a new class of crystalline materials constructed by metal centers/clusters and organic bridging ligands, which have received tremendous attention due to the fascinating structures and intriguing properties (Panella et al., 2006;M. T. Zhao et al., 2014). Their high pore volume, large surface area and tunable physicochemical properties make MOFs promising candidates for application in catalysis, gas storage, separation, drug delivery and analytical sensors (Liu et al., 2007; Decoste et al., 2012; Kumar et al., 2015; Ling et al., 2015). Recently, increasing interests have been focused on the development of functionalized MOFs-based EC biosensors. For instance, incorporation of porphyrin and metalloporphyrin moieties into the emerging porous MOFs materials can produce catalytic current and provide opportunity for the detection of different molecules including DNA, protein and lead ion (Ling et al., 2015; Xie et al., 2015; Cui et al., 2015). Besides, the signal of coordinated metal ions in MOFs can be directly detected in buffer solution (Shen et al., 2015; Liu et al., 2016). This differs from traditional signal tags such as quantum dots (QDs) and metal ions-encapsulated dendrimer which require acid dissolution and preconcentration (Zhang et al., 2011; Gao et al., 2013). Without such laborious operation, the MOFs-based detection steps are thus effectively simplified. Moreover, the easy incorporation of MOFs with metal nanoparticles paves the way to further combine with biomolecules which may be employed for target recognition and signal amplification. So far, the application of MOFs in DNA MTase assay has not been reported to the best of our knowledge.