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Scientists Explain the Role of DNA Methylation in Biological Activities

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Scientists Explain the Role of DNA Methylation in Biological Activities

March 18
03:05 2020

In the past years, people have increasingly realized the importance of DNA methylation research and developed a series of methods for detecting DNA.

Methylation is one of the main ways of regulating gene expression. Studying the methylation of chromosomal DNA is the basis for understanding gene regulation. After processing DNA with standard bisulfite methods, unmethylated cytosine C is deaminated to form uracil U. After PCR amplification, uracil U was replaced with thymine T, while methylated cytosine C remained unchanged. Based on a new generation of high-throughput sequencing platform, scientists perform low-cost, high-efficiency, high-accuracy mapping of the genome-wide DNA methylation level. The analysis of high-precision methylation modification patterns of specific species will surely have a landmark significance in epigenomics research, and will be used for the research of basic mechanisms such as cell differentiation, tissue development, animal and plant breeding, human health, and disease.

Biological effects of DNA Methylation

1. DNA methylation and genetic imprinting, embryo development

DNA methylation plays an extremely important role in maintaining normal cell function, genetic imprinting, and embryonic development. Studies have shown that the normal development of embryos benefits from proper methylation of genomic DNA.

For example, the lack of any methyltransferase is lethal to the development of mouse embryos (Li et al. 1992 and Okano et al. 1999). In addition, allelic repression is regulated by imprinting control regions (ICRs). One of the alleles in this region is methylated. Abnormal expression of imprinted genes can cause a variety of human diseases with mutations and phenotypic defects. Such as umbilical hernia-giant tongue-giant development syndrome (Beckwith-Wiedemann Syndrome, BWS) and Prader-Willi / Angelman syndrome, etc.

2. DNA methylation and tumors

Changes in methylation status are an important factor causing tumors, and these changes include a decrease in the overall methylation level of the genome and an abnormal increase in the local methylation level of CpG islands, leading to genome instability (such as chromosome instability, activation of mobile genetic factors, expression of proto-oncogenes) and non-expression of tumor suppressor genes. If the active allele in the tumor suppressor gene is inactivated, the risk of cancer is increased, for example, loss of the insulin-like growth factor-2 (IGF-2) gene imprint leads to many tumors, such as Wilm’s tumor.

Research on tumor methylation is currently focused on tumor suppressor genes. This is because studies found that tumorigenesis may be related to the methylation of CpG islands in the promoter region of the tumor suppressor gene and cause the tumor suppressor gene to be turned off. Because the local hypermethylation of CpG islands is earlier than the malignant proliferation of cells, the diagnosis of methylation can be used for the early prediction of tumorigenesis, and the genome-wide hypomethylation also appears with tumorigenesis. And it is significant with the increase of tumor malignancy, so the detection of methylation can be used for tumor classification.

Shinichi Toyooka describes the relationship between tumorigenesis and abnormal methylation: human mesothelial cells infected with SV40 (Simian Virus 40) have up-regulated telomerase activity, increased Notch-1 gene expression, and tumor-related genes (including the tumor suppressor gene RASSF1A). The promoter region is abnormally methylated. Cui et al. found that the IGF-2 gene signature of normal intestinal mucinous gland cells in some patients with colon cancer was lost. Uhlmann et al. found that seven tumor marker genes of glioma cells of different pathological types and different malignant degrees have different degrees of methylation. Therefore, the study of methylation provides a new basis for the early prediction, classification, classification and prognosis evaluation of tumors.

Research Methods of DNA Methylation

In the past years, people have increasingly realized the importance of DNA methylation research and developed a series of methods for detecting DNA. According to the purpose of the research, these methods are divided into methylation detection at the overall level of the genome, detection of specific site methylation, and search for new methylation sites. According to the different processing methods used in the research, it can be divided into methylation analysis method based on PCR; methylation analysis method based on restriction enzyme; methylation analysis method based on bisulfite and column layer method. Methylation analysis methods include HPLC-UV, LC-MS, ELISA-Based Methods, LINE-1+ Pyrosequencing, Levels of LINE-1 methylation and so on.

There are many advantages of methylation sequencing, for example, find methylation patterns of CpG, CHH, and CHG regions across the human genome, view methylation at almost every cytosine in the genome across most species with a genome-wide method known as whole-genome bisulfite sequencing, catch full sample differences with small amounts of DNA, cover emerging regions of interest in the human genome identified by ENCODE, FANTOM5, and the Epigenomics RoadMap Consortium with targeted methylation sequencing. Detection also include methylation microarrays, microarrays enable quantitative interrogation of selected methylation sites across the genome, providing high-throughput capabilities that minimize the cost per sample.

Creative Proteomics have a strict workflow to analysis methylation to meet your requirements.

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