Epigenetics environment and diseases Introduction Epigenetics is the manipulation above genetics it is the study of changing heritable phenotypes as a result of modified gene expression but without altering the DNA sequences Chemical modifications on chromosome DNA and structures can change the pattern of gene expression All cells in the body except erythrocytes contain identical DNA sequences the epigenetics allows the cells to develop into specific ones by changing the gene expression pattern Functions of each type of cells are determined by the pattern and therefore by epigenetics Epigenome is changeable as different genes are required during different periods throughout life As the cells communicate with one another signals from inside the cell neighbouring cells and environment allows the cells to know when and how they should change Importance of signals are dependent on the stage of development For example at the start of embryonic division after fertilisation signals from neighbouring cells provide information of which cell types they should be develop into environmental signals influence more on the epigenome in later development stages Sperm and egg cells contain epigenetic signals or tags from each parent respectively
These environmental factors can alter mechanisms that regulate gene expressions Environmental alterations to epigenetics can be beneficial or fatal Diseases such as cancer autoimmune disorders and mental disorders can be caused if gene expressions are altered DNA methylation DNA can be tagged by methyl groups Promoter DNA methylation is associated with silenced genes and it is important in maintaining cell types The process is carried out by DNA methyltransferases DNMT DNMT1 DNMT3a DNMT3b Embryonic development during fertilisation 3a and 3b are responsible for De Novo methylation differentiation allowing embryonic cells to develop into a cell type DNMT1 is for maintenance of methylation following differentiation and is active during cell division after differentiation Gene expression pattern and methylation pattern for each cell type is different Most CpG sites are methylated in humans but not the ones in promoter CpG island Promoter regions contain regulatory elements that control transcription of genes 3a and 3b obtain the methyl group from a molecule
SAM the methyl group is added to the fifth carbon on cytosine and forming 5 methylcytosine DNMT flips cytosine 180 degrees out of the strand then the DNMT enzyme obtains the methyl group from SAM and transfer it onto cytosine finally the methylated cytosine is flipped back Human TET enzyme that regulate DNA methylation patterns It adds a hydroxyl group onto 5 methylcytosine and make it become 5 hydroxymethylcytosine TET can also convert 5 gydroxymethylcytosine back to cytosine through several pathways TET is therefore thought to be responsible for DNA de methylation Both DNA methylation and de methylation are tightly regulated in development by DNMT and TET in normal human cells during development but this balance is disrupted in cancer cell causes a change in DNA methylation pattern There are hypermethylation in promotor region and this is associated in tumour suppressor gene inactivation Cancer DNA also undergoes wide spread hypomethylation in the entire genome This type of regulation is found in every type of human tumour This methylation pattern can be used to detect cancer cells from normal cells
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