Question

i) Describe the role of DNA methylation in eukaryotic gene expression.Within your answer explain how patterns of methylation are maintained
after DNA replication.

ii) With reference to single gene in mice, describe how diet can impact on DNA methylation and consequently the expression of that gene

Answer 1

i) DNA methylation is a process in which methly groups are added to DNA molecule. Methylation can be done at the bases cytosine and adenine, by changing the activity of a DNA segment without changing the sequence. It is required  for normal development and it involves processes like genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging etc. DNA methylation typically acts as a repressor or gene transcription. Both cytosine methylation and the removal of 5mC from DNA were associated in the control of cell differentiation. It has been shown that DNA methylation, in association with other regulators, is a major epigenetic factor influencing gene activities. The study of heritable changes in gene activity or function without any changes in the DNA sequence is called Epigenetics.

DNA methylation was catalyzed by DNA methyltransferases (Dnmts) that can transfer a methyl group from S-adenyl methionine (SAM) to the fifth carbon of of a cytosine residue to form 5mC. Besides, Dnmt1 copied the DNA methylation pattern from the parental DNA strand to the newly synthesized daughter strands during DNA replication. So, all the three Dnmts play an important role in the development of an embryo, and when the cells reach terminal differentiation, Dnmt expression will be reduced. This means that the DNA methylation pattern in postmitotic cells are stable but postmitotic neurons in mammalian brain are still showing some levels of Dnmts. So, Dnmts and DNA methylation may play a major role in the brain. DNA methylation is involed in the regulation of chromatin structure and promoter activity. It's function is to silence the promoters of imprinted genes showing monoallelic expression and the promoters of transposons, and contributes to gene silencing on the inactive X chromosome.

DNA methylation can occur rapidly through replication The hypomethylated newly replicated DNA made the maintenance DNA methylases to restore DNA methylation on the newly replicated DNA strand. DNA methylation is important in the preservation of genomic stability.

ii) Dietary components can also affect epigenetic eg. changing the pool of specific compounds available to the cell or influencing the activity of many enzymes. Epigenetic changes induced by dietary factor may vary from birth weight to cardiovascular disease. In mice, dysfunction of telomere, impaired proliferation and senescence, physiological imparment in many organ systems are some examples.