Functions of histone methylation

Everyone wants to be healthy and live a long life, so for many people, if they want to be healthy and live a long life, they must learn more health knowledge. Therefore, many people want to fully understand the function of histone methylation. In order for you to understand it in more detail, let’s take a look at the detailed introduction below. I hope you can learn more.

Function of methylation

Methylation is an important modification of proteins and nucleic acids that regulates gene expression and shutdown. It is closely related to many diseases such as cancer, aging, and Alzheimer's disease, and is one of the important research topics in epigenetics. The most common methylation modifications are DNA methylation and histone methylation.

DNA methylation can shut down the activity of certain genes, while demethylation induces the reactivation and expression of genes. DNA methylation can cause changes in chromatin structure, DNA conformation, DNA stability, and the way DNA interacts with proteins, thereby controlling gene expression. Studies have confirmed that methylation of cytosine in CpG dinucleotides causes more than one-third of genetic diseases in the human body caused by base conversion. DNA methylation mainly forms 5-methylcytosine (5-mC) and a small amount of N6-methyladenine (N6-mA) and 7-methylguanine (7-mG). In eukaryotes, 5-methylcytosine mainly appears in CpG sequences, CpXpG, CCA/TGG and GATC.

DNA methylation refers to the process in which an organism transfers a methyl group to a specific base group using S-adenosylmethionine (SAM) as a methyl donor under the catalysis of DNA methyltransferase (DMT). DNA methylation can occur at the N-6 position of adenine, the N-4 position of cytosine, the N-7 position of guanine, or the C-5 position of cytosine, etc. However, in mammals, DNA methylation mainly occurs at the C of 5'-CpG-3' to generate 5-methylcytosine (5mC)

In mammals, CpG exists in two forms: one is dispersed in the DNA sequence; the other is highly aggregated, which is called CpG island. In normal tissues, 70% to 90% of scattered CpGs are modified by methyl groups, while CpG islands are unmethylated. Under normal circumstances, CpG dinucleotides in the "junk" sequences of the human genome are relatively rare and are always in a methylated state. In contrast, CpG islands in the human genome, which are about 100-1000bp in size and rich in CpG dinucleotides, are always in an unmethylated state. CpG islands are often located near transcriptional regulatory regions and are associated with 56% of the human genome coding genes. Therefore, the study of the methylation status of CpG islands in gene transcription regions is very important. The results of the human genome draft sequence analysis show that there are approximately 28,890 CpG islands in the human genome, and most chromosomes have 5-15 CpG islands per 1Mb, with an average of 10.5 CpG islands per Mb. There is a good correspondence between the number of CpG islands and gene density.

DNA methylation is mainly catalyzed by the DNA methyltransferase family. Currently, three types of DNA methyltransferases (Dnmt1, Dnmt2, Dnmt3a, and Dnmt3b) have been discovered in eukaryotes. Dnmt1 is a maintenance methylase; Dnmt2 can bind to specific sites on DNA, but its specific function is still unclear; Dnmt3a and Dnmt3b are de novo methylases, which remethylate demethylated CpG sites, that is, they participate in de novo methylation of DNA. During the mammalian germ cell development and pre-implantation embryonic stage, the methylation pattern across the genome is reprogrammed through large-scale demethylation and subsequent remethylation to produce cells with developmental potential; during cell differentiation, the methylation state of the gene will be inherited by the offspring cells. Due to the close relationship between DNA methylation and human development and tumor diseases, especially the transcriptional inactivation of tumor suppressor genes caused by CpG island methylation, DNA methylation has become an important research topic in epigenetics and epigenomics.

Histone methylation refers to the methylation that occurs on the N-terminal Arg or Lys residues of H3 and H4 histones and is catalyzed by histone methyltransferases. The functions of histone methylation are mainly reflected in heterochromatin formation, gene imprinting, X chromosome inactivation and transcriptional regulation. In addition to the existence of histone methyltransferases, demethylases have now been discovered. Previously, people believed that histone methylation was stable and irreversible, but the discovery of this demethylase made the histone methylation process more dynamic.

The above content has given a detailed introduction to the functions of histone methylation. I believe that many people have understood the functions of histone methylation through the above understanding. Histone methylation has many functions, so for many friends who want to know more, they must be fully familiar with the above introduction, and then they will have more understanding of its functions.