5. Epigenomics and Proteomics Class (0610)
Epigenetics is the study of epigenetic variations which switch the gene expression by environment factor without affecting sequence of DNA. There are examples of epigenetic modification, DNA methylation, histone modification, and RNA interference.
1) DNA methylation
It is process which the methyl group is added to the DNA. When the promoter of gene is methylated, then it represses the gene expression. Adenine and cytosine can be methylated, adenine methylation occurs only in prokaryotes. DNA methyltransferase 1 is an enzyme which transfer methyl group to DNA, and they work as tissue specific manner. DNA methylation has important roles in mammalian system. Genomic imprinting, X-chromosome inactivation, Heterochromatin maintenance, Developmental controls, Tissue specific expression controls.
Genomic imprinting can be caused by DNA methylation, and histone methylation which is independent of Mendelian inheritance. Expression of gene is inherited from mother or father.
X-chromosome inactivation is the process which one of the two X chromosomes in all female cells is inactivated. Females(XX) carry twice as many dosage of gene as males(XY), so in order to solve this problem one X chromosome is inactivated randomly by methylations in the early developmental process in.
Chromatin can be found as two status, heterochromatin and euchromatin. Heterochromatin is tightly packed form of DNA, and controlled by DNA methylation.
As I mention above, DNMT1 act as tissue specific manner, so DNA methylation can control gene expression tissue specific manner.
2) Histone modification.
Basic unit of DNA packing is nucleosome which consists of DNA wound around eight histones protein. This histone octamer consists of two copies of H2A, H2B, H3, and H4. In the class, we think about why it consists of four different types, not simply one type. Jong said that it might be one type long time ago, but as we develop, more diverse regulation of gene expression might be needed. I agree with this and I think that H2A and H2B might be one type before, but as we need more regulation function, it might be differentiated into two similar types recently.
Histone modification is modification to the histone proteins. Because role of histone protein is packing of DNA, modification of it alters gene expression by regulating packing. At tightly packed DNA, transcription factor can’t easily bind to the DNA, so gene expression is down regulated. Modification includes methylation, phosphorylation, acetylation, ubiquitiylation, and sumoylation. It usually happens in the tail protruding from the histone core of the nucleosome, and also this modification site exits within the globular histone core. In the class, we think about why histone tail exists. I think that enzyme like DNMT1 can easily bind to the histone tail than histone core because histone tail is more accessible than histone core. I guess that that’s why the modification of histone tail is more common than modification of histone core.
There are many technologies for studying epigenomics. In the class I learned about bisulfate sequencing. When bisulfate is treated to the DNA, cytosine residues are converted to uracil, but 5-methylcytosine residues is not affected. By sequencing, we can know the methylated and unmethylated cytosine.
